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. 

 

Major Depressive Disorder (MDD) With Psychotic Features

This is a diagnosis that I often receive questions about. It can be confusing, how do we know if the person has schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features? 

They all have psychotic symptoms such as delusions and hallucinations.

In this video I’m going to explain how we navigate this diagnostic dilemma. 

For one to be diagnosed with MDD with psychotic features they must meet criteria for major depressive disorder based on the DSM-5TR. 

As a reminder, to meet criteria the person must have 5 out of 9 symptoms within a two-week period and at least one symptom must be either depressed mood or loss of interest

In medical school they teach you the mnemonic SIGECAPS, an interesting fact is this is written the way you would fill out a paper prescription for depression. SIG Energy Capsules which you would give to a person with major depression because of the low energy and loss of interest commonly seen in major depression. 

Anyway…

The other criteria include 

-Weight loss or weight gain 

-Insomnia or hypersomnia 

-Psychomotor agitation or retardation 

-Fatigue or loss of energy 

-Feelings of worthlessness or guilt 

-Poor concentration 

-Recurrent thoughts of death or suicidal ideation 

So, we have a person who meets criteria for MDD, they have 5 out of 9 symptoms for a two-week period. 

We should keep in mind it’s important that the person has also suffered some loss of function in their personal or professional life because of the symptoms. This is what makes it a disorder. 

Now, what if the person also has a loss of reality-based thinking in conjunction with the major depressive episode?

This will include things like delusions and hallucinations. The delusions can be persecutory in nature or paranoid, but other types may occur too. The persecutory delusions are ones where the person feels attacked or victimized by others. They may even believe people are coming into their home to harm them. This usually presents with the patient reporting things being moved in the home or things being out of place. A common paranoid delusion is one where the person believes they are being followed. This usually presents as a car or person the patient keeps seeing, and they cannot believe that it may just be a coincidence, or someone who travels the same route to work every day.

Delusions are fixed false beliefs, and although there may be rational explanations for the things going on around them, this is the patient’s reality, and you must be careful when challenging it. The belief is fixed, and That is why presenting evidence contrary to the belief is not effective.  

The important point here is the psychotic symptoms are only present during the major depressive episode. Treat the depression and the psychotic symptoms resolve. If the psychotic symptoms remain after the major depressive episode is successfully treated, you need to reevaluate the diagnosis.

This is what separates MDD with psychotic features from schizophrenia. 

In bipolar disorder with psychotic features, the psychosis often occurs in the manic phase of the illness and has a grandiose theme associated with it. The patient my for example believe they are a prominent religious figure, or the government is plotting against them. 

We often call the delusions in depressive episodes mood congruent, meaning they are consistent with how the person is feeling. It’s not a far stretch for a person who is severally depressed to feel like people want to harm them. 

Treatment

Treatment is well established and consists of an SSRI or other antidepressant medication in combination with a dopamine blocking medication. The other option is electroconvulsive therapy (ECT) when the person is severally depressed not eating, attending to ADLs, or at risk for suicide. 

Patients should remain on medication for at least 6 months after complete resolution of symptoms. This is very important as relapse has been proven to occur when medication is stopped prior to that time. People can taper off the dopamine blocking medication after 6 months as these tend to have worse side effect profiles. The SSRI should be continued for 1 year at which time you can attempt to taper off or reach a lowest effective dose if symptoms begin to reappear. An index phase of ECT should be completed if that is the treatment of choice which consists of 12 total sessions done either 2 or 3 times per week. 

Malingering In Psychiatry

  • Let’s first define malingering, this is the production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives. 
  • Not all lying involves secondary gain, but ALL malingering does involve secondary gain 
  • Common secondary gains include avoiding military service, avoiding work, financial incentives, avoiding legal actions, and obtaining controlled substances 
  • Feigning mental illness is not the same as malingering because the reason behind the false production of symptoms is not assumed with feigning symptoms. 
  • Factitious disorder is the voluntary production of symptoms, but this is with the goal of assuming the sick role or role of a patient, it’s not done for secondary gain. 

Consider malingering when….

-Rare symptoms are present 

-Improbable symptoms are being reported

-Rare combination of symptoms are present

-Reported Vs observed symptoms are not congruent

Malingered Depression:

-25-30% of patients who claimed major depression in civil litigation were probably malingering

-Pay careful attention to facial expressions 

-Pay careful attention to motor function, psychomotor retardation is an important observable sign

-If appetite changes are reported look for actual objective weight change 

-symptoms opposite of depression 

-blaming others for everything is not the way guilt typically presents in depression, this is externalizing and not taking personal responsibnility

Malingered Psychosis: 

-Often in true psychosis people can describe the voice/s, is it loud, soft, male, female, you have some experience of what you heard. When you ask a malingering patient about a voice, they should have some ability to describe what they are hearing, if not consider malingering.

-If you are suspicious, begin with open ended questions, ask them to describe things in their own words. 

-Genuine AH are in words or sentences, drug Hallucinations usually occur as unformed noises.

-The location of the voice inside the head or outside is no longer a good predictor of malingering 

-Many times the content of voices are derogatory in nature

-Other signs of malingered psychosis include Vague or inaudible auditory hallucinations, AH not associated with delusions (86% of AH have an associated delusion), no strategies to diminish voices 76% of patients have some coping strategy to diminish the voices. They claim that all instructions are obeyed, the hallucinations are visual alone, seeing little people or giant people for example.

 

The Loneliness Epidemic and Avoidant Personality Disorder 

Although loneliness has always been a friend of mine (Backstreet boys 1997), there is an epidemic of loneliness across all age groups. 

We live in a world where we are all more connected with each other through technological advances and social media, yet people feel more disconnected than ever. 

The COVID-19 pandemic did make this any better, 36% of all Americans, including 61% of young adults and 51% of mothers with young children feel loneliness is a significant problem in their lives. 

The question is are people feeling lonely because they are suffering from avoidant personality disorder?

Epidemiology

The prevalence of APD is 2.36% in the general population, and it appears to occur equally in males and females. 

Definitions and Criteria for diagnosis

Let’s start with a definition of what avoidant personality disorder is and how it can impact a person’s life. 

This is part of the cluster C personality disorders often thought of as the anxious/fearful personality disorders. These individuals experience excessive social anxiety, severe feelings of inferiority and inadequacy, and while they desire close relationships, they avoid the feared stimulus instead living in self-imposed social isolation. 

Other key criteria include: 

-patterns of social inhibition 

-hypersensitivity to rejection or criticism 

-it must be present by early adulthood 

This affects all areas of life and should be a pervasive pattern. It’s not something that is isolated or situational.  

DSM-5 Criteria: 4 out of 7 are required to make a diagnosis 

  1. Avoids occupational activities that involve significant interpersonal contact because of fears of criticism, disapproval, or rejection. 
  2. Unwilling to engage in relationships unless they are certain of being liked. (They will look for social cue or indicators of interest before committing and often attempt to read other minds) 
  3. Shows restraint in relationships for fear of being ridiculed or shamed 
  4. You are preoccupied with being criticized or rejected 
  5. The person is inhibited in new interpersonal situations because of feelings of inadequacy 
  6. The person will view themselves as socially inept, inferior to others, or unappealing to others. 
  7. The person is reluctant to take personal risks for fear of embarrassment 

It’s important to keep in mind this diagnosis is largely unchanged since DSM-III and are primarily viewed through a psychoanalytic lens. The key difference between avoidant personality disorder and social anxiety is these feelings are pervasive throughout the person’s life, where in social anxiety they are limited to social situations. Although some believe these are the same disorder with many of the criteria overlapping. Avoidant patients tend to read more into things and are constantly looking for any indication from others that supports their theory that they are defective or inadequate. 

Other personality disorders can have rejection sensitivity and sensitivity to criticism, this is often seen in narcissistic personality disorder. We are all sensitive to criticism in certain situations it’s not necessarily pathological. 

Treatment: 

This largely focuses on psychotherapy and sometimes medication if other comorbid psychiatric disorders are identified. Some of the psychotherapy techniques that are effective include social skills training, cognitive behavioral therapy, and exposure therapy. These are also good cases for psychoanalysis if the person can commit to that form of therapy. 

Conclusion :

Could Some of the Loneliness people are experiencing be due to avoidant personality disorder?

-Possibly, but it’s only going to be a small percentage considering the prevalence of avoidant personality disorder is 2.36%. 

-Loneliness has many contributing factors and encouraging people to spend less time connecting digitally and more time connecting face to face is a good place to start. 

How to Manage Aggression with Psychopharmacology in an Inpatient Setting

I’m very careful about the content I consume and the resources I use to grow as a psychiatrist.

When I endorse something like The Psychiatry & Psychotherapy Podcast, you know it’s something I personally use and trust. 


I had the opportunity to work with Dr. Puder on a recent episode How to manage aggression with psychopharmacology in an inpatient setting. Unfortunately, I got caught up taking care of patients on my inpatient service on the day of the recording and did not get to talk with Dr. Puder and Dr. Cummings.

I would encourage you to listen to all the episodes, but my personal favorites are the ones with Dr. Cummings. He has a wealth of knowledge and I’ve learned some amazing clinical pearls that I apply in my daily practice. 

Check out the episode, you will not be disappointed

https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-145-how-to-manage-aggression-with-psychopharmacology-in-an-inpatient-setting

Can Benzodiazepines be Prescribed Ethically?

Benzodiazepines are quickly gaining a reputation as the new opioids in terms of risk for abuse and potential for adverse events. The question remains, is there a way to ethically prescribe these medications to patients while reducing the risk of abuse? 

Medication Side Effects: Doctor my mouth is a little dry

Regular Dental Care and Oral Hygiene

Dry mouth is another common side effect from psychiatric medication. Patients on psychiatric medication often have poor dental care and poor dental outcomes. There is increased incidence of dental caries and oral ulcers in this population. This patient population is also three times more likely to lose all their teeth. Let that sink in for a moment. Now some of this is related to not following the recommended dental hygiene guidelines such as regular cleanings at least every 6-months. Thus, this is the first step in the process. Ensure the patient first has a dentist, and second be sure they are making regular 6-month appointments, and if they have issues with dental health, they should be going for cleanings as often as every 3 months. Oral hygiene is the foundation for the remainder of the interventions.

Gum, Candy, and Pilocarpine

Most patients are told to carry a bottle of water around and take frequent sips throughout the day. This does not work. It provides temporary relief, and does not address the underlying issue. You can educate the patient about drinking more water while eating which can help facilitate the swallowing process especially when dry mouth is an issue. Carrying a cup of ice can be helpful but is not convenient. What I prefer is the use of sugarless gum or candy which can be easily carried and chewed as needed. Studies have demonstrated that xylitol containing gum can reduce the levels of Mutans streptococci and lactobacilli in saliva and plaque. This has the potential to reduce the incidence of dental caries, and is an inexpensive option for most patients. I will also recommend as a second line using a mouth wash for dry mouth such as Biotene. If these interventions are not effective a medication to stimulate saliva production such as pilocarpine. In many cases pilocarpine eye drops which act locally is a better option than a medication that acts systemically. 

Final Words

Dry mouth is a common side effect patent’s experience but may not always bring to the clinician’s attention. There are interventions to treat this side effect that range from simple interventions like xylitol containing gum to pharmacological interventions such as pilocarpine eye drops. Most patients will experience relief with the above treatments. This highlights the importance of asking about specific side effects so they can be treated early and prevent long term Complications such as tooth loss. 

Diagnosis Depression: Sleep Dysregulation

One of the most common symptoms found in multiple psychiatric disorders is sleep disturbance. In fact, sleep disturbance is one of the criteria for the diagnosis of major depression. This post will offer an explanation of some of the changes observed in the sleep patterns of depressed patients.

Much of this information comes from sleep studies in patients who have a diagnosis of major depressive disorder. Without getting too technical there are two primary types of sleep, non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM). The NREM sleep can be broken down further but for the sake of simplicity we will consider these two categories. 

What we notice in sleep studies of patients who suffer from major depression is a much faster onset of REM sleep. The body usually cycles through these stages 4-6 times throughout the night, averaging 90 minutes in each stage. As the night progress NREM sleep decreases and REM sleep increases. A person with normal sleep architecture will enter REM after 90 minutes, in patients with depression this time period is shorter and can be observed on the sleep study results.

Other changes include decrease NREM sleep which can be thought of as restorative sleep. Increased REM density reduced total sleep time, and decreased sleep continuity are also present. 

Any single change in sleep architecture is not diagnostic of major depression. However, taken together decreased onset to REM, increased REM density, and decrease sleep efficiency can separate patients with major depression from a control group. 

Given all of this information, routine sleep studies are not diagnostic for major depression and are not routinely ordered unless you suspect another sleep disorder. 

Hopefully this provides a basis for why questions about sleep in depressed patients are important. The sleep changes also provide some objective evidence of altered sleeping patterns in patients with depression. 

What’s Your Therapy

The other day, I was working out in my home gym and I started to think about the topic of therapy. Most of my thinking is done in the solitude of the gym. I keep a small pad and pen to write my thoughts down in between sets. On this particular night, I began thinking about what my own therapy looks like.

The things I was thinking about were not necessarily the standard type of talk therapy most people are accustomed to. I absolutely believe in talk therapy. Honestly, every psychiatrist should be in therapy and it’s often recommended to trainees. The work of a psychiatrist is deep emotional work and its good to analyze these experiences with someone. However, it’s not always easy to find a good therapist.

People often wonder outside of formal talk therapy, what activities do psychiatrists use to reduce stress. 

My personal form of therapy is physical training. I learned a lot about myself over the years by demanding a lot of my body. I stress to all of my patients the importance of self-care in the form of physical activity. The human body is made to move, and we have slowly grown into lives of inactivity. Much of our work, education, and leisure activates involve no physical movement. I highly recommend incorporating various sports, running, weight training and other fitness actives into your daily life. If you can bring a friend along for the workout even better. This covers both physical and social areas of wellbeing. 

This biggest barrier to this process is getting started. Patients often say, “I could never do that” to which I say you don’t have to. Start off simple call a friend or two that can serve as workout partners and start with one 20-minute walk per day. It’s low impact and can be accomplished in almost any setting. There is no need to invest in the best pair of running shoes, a gym membership, or personal trainer. It’s about creating a sustainable habit that will continue for a lifetime. All you need to do is literally take that first step. 

Feel free to share what helps you stay mentally fit and reduce stress in the comment section below.

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