Friday, 15 April 2011

Paranoia: Prevalence and Correlates


Clinicians dealing with psychiatric disorders commonly encounter patients with paranoia in their clinical practices.  However, it is important for clinicians to understand the relatively frequency of paranoia endorsement by people in the general population.  Whether paranoia is a pathological phenomenon commonly depends on the degree of paranoia, associated signs and symptoms and presence (or absence) of a formal psychiatric diagnosis.  Freeman and colleagues from the Institute of Psychiatry other colleagues in London published an important paper to address this issue.

Their data and research stems from a general population study of over 7,000 general population survey respondent in England.  To assess paranoia in the general population, subjects were asked three questions where positive responses reflected increasing severity of paranoia.  The three questions in the survery (and the general population rate of endorsement) were:

  • Paranoia level 1. ‘Over the past year, have there been times when you felt that people were against you?  (18.6%)
  • Paranoia level 2. ‘In the past year, have there been times when you felt that people were deliberately acting to harm you or your interests ? (8.2%)
  • Paranoia level 3. ‘In the past year, have there been times you felt that a group of people was plotting to cause you serious harm or injury?  (1.8%)
I found it interesting the relatively high rate of endorsement of paranoia level 1 in the general population.  Nearly one in five endorsed feeling times in the last year when they felt that people were against them.  As the severity of paranoia increased, the prevalence rates decreased to less than 2% of the population fealing a good of people was plotting to cause them harm or injury.

The research also looked at some of the correlates of paranoia.  Those endorsing each level of paranoia were compared to those with no endorsement of paranoia.  The paper is packed with data but here are some of the things that stood out for me:

  • Level 1 paranoia was more likely to be endorsed by women while level 3 paranoia was more likely to be endorsed by men
  • Paranoia rates were higher in populations with a variety of medical conditions including: diabetes, hearing or visual problems, recent heart attack/angina.  There was a trend for increased level 3 paranoia in those with obesity (BMI greater than 30 kg/m2)
  • Paranoia rates were higher in a variety variables indicating social isolation, i.e. separated, divorced or single marital status, fewer number of close family members or friends, fewer supportive relationships
  • Paranoia rates were higher along with a variety of other psychiatric symptoms/disorders, i.e. insomnia, depression,worry, anxiety, panic and PTSD
  • Paranoia rates were increased in those endorsing suicidal thoughts in past year, history of a suicide attempt, anxiolytic and antidepressant drug use and not surprisingly antipsychotic medication use
  • Paranoia rates were strongly and progressively associated with cannabis use and less strongly associated with heavy drinking
In summary, this research manuscript provides a valuable overview of paranoia.  Elements of paranoia are relatively common in the general population.  Paranoia is a marker for many other psychiatric syndromes and cannabis abuse.  Clinicians should include screening questions for paranoia in routine clinical assessment.

Photo of Japanese Maple Courtesy of Yates Photography

Freeman, D., McManus, S., Brugha, T., Meltzer, H., Jenkins, R., & Bebbington, P. (2010). Concomitants of paranoia in the general population Psychological Medicine, 41 (05), 923-936 DOI: 10.1017/S0033291710001546

Thursday, 14 April 2011

Nicotine Replacement in Schizophrenia

Inpatient psychiatric hospitals increasingly prohibit smoking by patients, staff and family in their units.  Although the public health benefits of smoking restrictions are undeniable, there may be some situations where smoking restrictions have unintended consequences.  One area is the emergency management of patients with serious psychiatric illnesses such as schizophrenia and bipolar affective disorder.

Rates of smoking have been documented to be higher in both schizophrenia and bipolar affective disorder.  The likelihood is high that acute psychiatric emergencies in schizophrenia and bipolar will be accompanied by nicotine dependence.  Clinicians are left making a decision on how to manage nicotine dependence in the context of psychotic decompensation.

Michael Allen and colleagues recently conducted a small study of nicotine dependence management in forty subjects with schizophrenia admitted to a psychiatric emergency service.  Subjects were required to be smokers at the time of admission.  Severity of smoking dependence was assessed using the Fagerstrom scale.  Subjects received standard antipsychotic therapy without restriction but they were randomized to receive either nicotine replacement therapy (21 mg nicotine patch per day) or placebo patch.

Here is a summary of the results of the study:

  • Nicotine replacement reduced a measure of agitation by 33% in the first four hours and 23% at 24 hours
  • This reduction was statistically significantly more than with antipsychotic alone and placebo
  • Subjects with lower nicotine dependence scores tended to show the most response compared to placebo
  • The size of the effect of nicotine replacement on agitation reduction approached the level seen with standard antipsychotic therapy

So the beneficial effects of replacing nicotine in the short term in this population is pretty dramatic and of signifcant magnitude.  The authors note that it is possible the 21 mg nicotine patch is insufficient to address nicotine withdrawal in schizophrenics with more severe nicotine dependence.  Since the nicotine patch typically takes several hours to provide significant blood levels, the authors suggest a combination of nicotine gum (with rapid onset) and a patch may be the best strategy.

Encouraging patients with psychotic disorders and mood disorders to quit smoking is an important general health strategy.  However, this study suggests that attempting this during an acute psychotic break is probably counter productive and may be inhumane.  Acute nicotinie withdrawal may exacerbate the agitation of psychosis.  Nicotine withdrawal attempts in this population is probably better suited for periods where psychotic symptoms are under control.  It also makes sense to monitor patients with schizophrenia closely during attempts to stop smoking.  This period may be one of increased risk of psychiatric decompensation.

Photo of Nicotine Patch Courtesy of Wikipedia Creative Commons by RegBarc

Allen MH, Debanné M, Lazignac C, Adam E, Dickinson LM, & Damsa C (2011). Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study. The American journal of psychiatry, 168 (4), 395-9 PMID: 21245085

Wednesday, 13 April 2011

Gluten-Free Whole Grain Artisan Bread & Raw Kale Salad

I have been trying to create a beautiful loaf of gluten-free whole grain artisan bread for weeks now.  Finally after many tries, and  with some help from Artisan Bread in Five Minutes a Day I accomplished it. Check out their website for good step by step pictures. They use eggs in their recipe and I replaced them with flax eggs. I baked the loaves in my "La Cloche" at 500 degrees for 30 minutes, but you can also bake it in a dutch oven like the website showsMake sure you follow the instructions perfectly because gluten-free bread is not as forgiving as regular breads.  If you let it rise longer than the stated amounts, it will actually start to deflate.  Also, you need parchment paper to put your loaf on when rising the second time and when cooking.  You can carefully move the parchment paper with the gluten-free loaf of bread into the La Cloche without much movement or destruction to the size. Serve this delicious gluten-free artisan bread with a big raw kale salad. (recipes below).  See this link for my Whole Wheat Raisin-Walnut Artisan Bread and check out Breatopia for some good videos on making all different types of Artisan Bread.

Gluten-Free Whole Grain Artisan Bread
Makes 2 loaves

1 cup Brown Rice Flour
3/4 cup Sorghum Flour
1 1/2 cups Tapioca Flour (also called tapioca starch)
1 tablespoon yeast
1 tablespoon sea salt
1 tablespoon Xanthan Gum
1 1/3 cups lukewarm water
4 Tbsp. ground flax seed mixed with 6 Tbsp. water (should equal 1/2 cup)
2 Tbsp. extra virgin olive oil
1 tablespoon raw agave
sesame seeds to sprinkle on top of loaf (optional)

1.) Mix  the flours, yeast, salt and xanthan gum in a bowl.  Combine the oil, agave and water, set aside. Mix the flax seed and water together with spoon until egg like. Dump the flax seed mixture into the dry ingredients and then stir while you pour in about 1/3 of the oil and water mixture.   Continue to stir while you pour in another 1/3 of the liquid.  The dough will start to come together in a thick dough.  Add the final 1/3 of the liquid and stir until the dough is nice and smooth. 

2.) Cover the bowl with a shower cap or plastic.  Allow it to sit on the counter for 2 hours. Get a glass of water and wet hands before removing dough from bowl. Divide into half  for two loaves.  Place each piece on parchment paper and shape into a round ball.  Smooth with water until it is smooth.  Cover loosely with plastic wrap and allow to rest on the counter for about 90 minutes. 

3.)  30 minutes before baking time preheat oven with either a 5 1/2 quart Dutch Oven or a La Cloche to 500 degrees. The dough will not have grown much while resting, but it will seem a little bit puffier.  Use a serrated knife to gently cut slashes on top of the bread.  Sprinkle with sesame seeds and place parchement paper with bread in Dutch Oven or La Cloche with lid on.  Bake for 20 minutes and then remove lid.  Reduce oven temperature to 350 and cook another 15 minutes.

4.)  Remove from oven and allow to cool before slicing. 

6.)  This loaf is also wonderful toasted and served with jam or Earth Balance Butter. 


Raw Kale Salad

1 bunch of curly kale (remove rib)
1 tsp. extra virgin olive oil
1 tsp. sesame oil
2 tsp. raw Nama Shoyu or Bragg's liquid aminos
1 Tbsp. raw sesame seeds
1 tomato (diced)

1.) To prepare kale remove the tough center stalk by pulling the leaves off of it. Then wash the kale and  break into smaller pieces.

2)  Add all ingredients in bowl except sesame seeds and tomato.  Message kale leaves until soft and reduced in size. Add sesame seeds and diced tomato and mix well.  Serve or store in refrigerator until ready to eat. 

Ecstasy Acute Effects on Social Cognition


MDMA (Ecstasy) Chemical Structure

Anecdotal reports suggest that some users of ecstasy (3,4-methlenedioxymethamphetamine-MDMA) experience increased feelings of empathy and are more social while under influence of the drug.  Such effects may contribute to the timing and frequency of ecstasy use and may also contribute to risk of abuse or dependence.  Understanding this phenomenon in more detail might provide clinicians with better strategies to reduce use and the associated complications of ecstasy use.

Studying acute effects of illicit drugs is difficult under natural conditions.  Users of ecstasy commonly also use alcohol, nictoine and other illicit drugs in the context of ecstasy use.  Isolating psychological effects of one agent in this type of environment is difficult if not impossible.  One alternative is to admiinster ecstasy in a laboratory setting with subjects blind to whether ecstasy or placebo is being administered.  However, this approach poses significant ethical challenges.  One approach, is to limit human study in the lab to those who have previously use ecstasy and intend to continue using.  Although imperfect, this approach limits risk of exposing ecstasy naive individuals to an illicit drug that may have reinforcing effects and increase risk of future drug use.

Chemical Structure of Methamphetamine
A study in Biological Psychiatry took this approach when over four sessions, healthy ecstasy using volunteers received either a low or high dose of MDMA, a dose of methamphetamine (METH) or placebo.  MDMA and methamphetamine share chemical (see chemical structures), pharmacological as well as psychological features.  Methamphetamine is typically considered a compound that increases CNS dopamine and norepinephrine while MDMA is felt to also increase CNS serotonin.   Ratings on a series of psychometric measures were obtained over a period of six hours after drug administration.  Visual analog scales (VAS) rated subjective feelings in a variety of domains: stimulated, bored, sedated, anxious, insightful, nauseated, loving, dizzy, sociable, confused, lonely, elated, playful, blank and restless.  Additionally, the rated themselves on the 72-item Profile of Mood States (POMS).  Subjects also completed a facial affect recognition task where they were asked to identify four facial emotions: anger, fear, happiness, sadness.

Here is a summary of the study findings for active agents compared to placebo:
MDMA (high dose) increased subjective VAS ratings of feeling "loving" and "friendly"
MDMA (low dose) increased subjective VAS ratings of "lonely"
MDMA (high dose) and METH increased VAS ratings of "playful"
METH alone increased VAS ratings of "sociability"
MDMA (high dose) reduced the accuracy of recognizing angry faces

So there is some support in this study for the anecdotal reports of increased prosocial cognition with MDMA.  The authors note their findings suggest MDMA increases social approach (sociability) rather thanThe authors note the study supports the possibility that increased social behavior with MDMA might be due to a reduced sensitivity to negative emotions of others rather than increasing recognition of positive emotions in others.  There also might be danger with this effect as social risk taking might increase potential for adverse consequences (connecting with someone you would be unlikely to connect with when not under the influence of MDMA).

Chemical structures of MDMA and methamphetamine from Wikipedia Creative Commons authored by Harbin.

Bedi G, Hyman D, & de Wit H (2010). Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biological psychiatry, 68 (12), 1134-40 PMID: 20947066

Tuesday, 12 April 2011

Phentermine/Topiramate Combo for Obesity

Molecular Model of Topiramate
Previous Brain Posts summarized some of the pharmacologic agents in the pipeline for weight loss as well as some drug combinations.  A recent research study published in Lancet provides additional data on one of the drug combinations being studied: phentermine and topiramate.

This new study is important because it looked at 56 weeks of treatment and target obese individuals with at least two obesity-related medical complications.  Subjects were required to have significant obesity (BMI 27-45 kg/m2) and at least two of the following:  hypertension, dyslipidemia, diabetes or prediabetes, abdominal obesity).  Each of these factors increases the risk of mortality associated with being overweight.

The key findings from the study--number of pounds lost at 56 weeks:

  • placebo-- 3.1 pounds (1.4 kg)
  • phentermine 7.5mg/topiramate 46 mg-- 17.8 pounds (8.1 kg)
  • phentermine 15.0mg/topiramate 92 mg-- 22.4 pounds (10.2 kg)

The weight loss outcome in the highest dose group was approximately 10% of body weight--a significantly positive result in light of previous single agent trials.

One area of outcome caught my eye, the change in physiological and metabolic parameters over the course of the study.  Waist circumference decreased about an inch (2.4 cm) in the control group but three (7.6 cm) to three and one half inches (9.2 cm) in the low dose and high dose treatment group.  Blood lipid changes were also pretty impressive with LDL and triglycerides falling more in the treatment groups while good cholesterol values (HDL) increased more with the active drug combination.  Fasting insulin levels dropped significantly more in the active groups also.

Given historical problems with use of weight loss drugs, safety issues are important to monitor closely.  The most common adverse events in the active agent groups with rates higher than placebo were dry mouth (21%), paresthesias (numbness and tingling) (21%),  constipation (17%), dysguesia (10%), insomnia (10%), dizziness (10%), anxiety (4%) and irritability (3%).  Although infrequent (1%) depression was noted in the high dose group more than placebo.  One potential red flag with this combination was report of 11 cases of renolithiasis (kidney stones) in the high dose active agent group.

Topiramate inhibits the action of carbonic anhydrase.  This effect can cause decreases in serum bicarbonate and potassium as well as increasing risk of renolithiasis.  The rate of renolithiasis was lower in the low dose group suggesting a dose-related effect.  Additional, inhibitors of carbonic anhydrase have been noted to cause alterations in sensation (paresthesias) and in taste (dysguesia).

The authors note several relevant areas of caution.  Subjects with clinically relevant depression were excluded from the study due to concern about drug-induced depression.  Also some subjects noted cognitive adverse events, attention or memory problems, and this needs to be monitored in those more prone to such effects.  Additionally, the first application to approve this combination of phentermine and topiramate was turned down for lack of long-term cardiac safety data and data on risk of use during pregnancy.  This additional data is likely being collected for analysis and possible re-application given the impressive level of weight loss associated with this combination.

Molecular model of topiramate from Wikipedia Creative Commons, Author fvasconcellos.

Kishore M Gadde, David B Allison, Donna H Ryan, Craig A Peterson, Barbara Troupin, Michael L Schwiers, Wesley W Day (2011). Eff ects of low-dose, controlled-release, phentermine plus
topiramate combination on weight and associated
comorbidities in overweight and obese adults (CONQUER):
a randomised, placebo-controlled, phase 3 trial Lancet : 10.1016/S0140- 6736(11)60205-5

East West Healing on Blogtalk Radio

Hey, it's that time again.  Join me and Josh and Jeanne Rubin from http://www.eastwesthealing.com/ at 4pm Eastern time this afternoon for a continuation of our first conversation a few weeks back.  I hope to bring up some of the general myths about insulin resistance and related topics...

CLICK HERE TO LISTEN 

Monday, 11 April 2011

Traditional Diets


This week is shaping up to look like diet week, where we examine a handful of popular diets or concepts in greater depth. In a sense, much of it will be review for the long-time followers. My hope is that it will get the attention of the people that are following some of these diets, being told that they are the best thing since sliced, gluten-free bread, and suffering some of the common and easily-identifiable consequences of being on such diets. We start with the broad concept of “traditional diets…”

Old habits die hard. One that I’ve found hard to kill, and still see others referencing with far too much enthusiasm, is the ol’ tradition-o-philia. Perhaps it was my own over-reliance on traditional diets as a tether in arguments, perhaps it is something else. But, I must say, this traditional diet concept is very limiting, misleading, overly worshipped, and in many ways foolish. So I propose a new rule – stop talking about traditional diets.

Seriously, if I hear “Masai” or “Kitavan” one more time I might scream. Or at least run to the nearest McDonald’s.

While it’s always of great interest that there were many traditional peoples that had excellent markers of good physical development such as great teeth and skull formation, and that these excellent indicators eroded with the sudden introduction of refined foods like white sugar and white flour, the past really needs to be left behind.

Anyone tried the Masai diet? I did - or at least I came pretty close eating only milk for nearly a month. It sucked ass, I had extreme allergies to everything and severe chest pain after only 27 days – plus it was not fun. I’d much rather eat whatever the heck I want out of convenience and go to the dentist for repairs than do that for life. “Oh, but it was the quality of the milk!” Perhaps, but that was about the best quality any reasonable person could find or afford without buying their own cow and farm. In today’s society, nothing about that is really functional even if it did give you some magical health like the Masai who, even with great health, don’t exactly live to be 100 years old. So it’s rather pointless to imitate.

How about the Kitavans? Who is going to wake up to a breakfast of boiled yams, a lunch of fruit, and a dinner of more yams, greens, and a little fish… maybe some coconut thrown in here and there – 365 days per year for the rest of their lives? Chirp, chirp, chirp.

When discussing traditional diets, the word “irrelevant” sneaks in with ever-increasing volume.

There are so many other variables as well. For example, one argument that I recently came across in the book Deep Nutrition (ironically about traditional diets mostly), goes something like this…

A mother smoking during pregnancy is known to increase the risk of asthma in the child. The author’s logic goes something like this…

1) Mother is breathing in a bunch of toxic chemicals, convincing the body that the world the baby is about to come into is full of pollutants.

2) Initiates the pulling of a set of epigenetic and hormonal levers that prepares the baby for the world the body thinks it’s about to enter into.

3) Baby is born with a hypervigilant response to airborne material for heightened protection against airborne threats.

Of course, this is just one example. I think most mothers in the modern world, just because of the nature of the modern world, are under a lot of stress and inflammation. Compounding this is the fact that the cells and tissues of modern humans are overloaded with the building blocks for inflammation – Linoleic acid and Arachidonic acid.

But what I’m saying is that a baby with that heredity is fundamentally very different from someone living in a traditional society. That person has very unique dietary and lifestyle requirements, all of which should be geared up to minimize stress and the production of inflammation. That person cannot go and run a billion miles like such and such tribe, or eat a lot of overtly inflammatory foods like French fries. He or she certainly can’t go on a standard low-carb diet, which requires much greater demand from the stress system.

Taking a deeper look down this same hole, the human genome literally undergoes massive changes in response to diet, trying to prepare the infant for the world it is entering into. Traditional peoples were in synch with their environment, eating the same general diet generation after generation. Even if they did eat a diet that was stressful such as the diet of the Eskimo, it was consistent enough and with enough regularity and nutritional excellence for them to adjust their epigenome to the diet. Modern humans trying to mimic this diet without having the proper hereditary blueprint for it (something one can only acquire by having Eskimos as parents), yields disaster.  It's very plausible that any drastic departure in diet from what your parents ate could backfire and make your health worse, not better. 

This brings up a couple more important points. For starters, the Eskimo, while they had great teeth and no signs of heart disease, still aged rapidly. I’m not talking died young because they starved to death or got bitten by polar bears, but aged rapidly (reported as looking a lot older than they were and dying of natural causes at very young ages – typically 60’s and 70’s). Harsh climate, low sunlight over the winter, a diet lacking carbohydrate, high in polyunsaturated fat – this will age ya quickly. No one should be infatuated with this diet.

Secondly, traditional diets the world over were generally VERY specific. Nowadays you have people saying, “oh, the Eskimos didn’t eat carbohydrates, so it’s safe to do the Atkins diet.” The Eskimo boiled whole fish, which contains thyroid hormone. They ate copious amounts of rotten fish, potentially full of short-chain fats that a normal low-carb dieter wouldn’t get. They subdivided the adrenal glands of animals amongst tribe members to get adequate vitamin C. Their diet was seasonal, synchronizing their diet with the current environmental demands. They relied in large part upon intuition when eating. They didn’t starve themselves when hungry after a long day because eating extra food wasn’t on their diet plan. These are all very specific things that people don’t take into account when they just decide to eat nothing but ribeye from Wal-Mart for a few years. And a misstep on any one of those important factors can be the difference between health and destruction. Traditional diets are simply too area and tribe specific and restrictive to be mimicked in today’s world.

Restraint and restriction is another important and underappreciated aspect of trying to eat a traditional diet – whatever that is. The human brain and emotions are extremely complex and powerful, potentially having more of an influence over one’s health status than the quality of their diet in many cases. Trying to eat a strict diet when you are surrounded by tempting other options is not something traditional peoples had to deal with. The food they had was all they knew, so as long as supplies were adequate, they knew not deprivation. But the feeling of deprivation or wanting something and not providing it to your body are powerful triggers of physiological changes within your body – namely catapulting your body into a hibernatory, low metabolic state.

Of course, we shouldn’t discredit all elements of traditional food eating. I think the main lessons that can be gathered and banked on are that they ate the whole animal, ate whole foods, never ate a vegan diet, and ate foods with a high nutritional value in terms of vitamins and minerals. These are great fundamentals. However, complexity still remains. Eating the whole animal is something that is impractical for some, many lack the skills, abilities, knowledge, and equipment to “cook the whole animal,” many can’t conveniently acquire whole animals, and many see the brains and liver and eyes and such as yucky. Trying to force down unpalatable food is a health liability as far as I’m concerned, and studies have indicated that eating something that’s not enjoyable reduces mineral absorption from that meal.

Traditional peoples, while they had excellent health, were still not some magical pinnacle of human health and longevity. They should not be worshipped as if they lived to be 700 years old. They didn’t. Many aged just as quickly as we do. Many aged much faster. With modern science we can see precisely what type of diet and lifestyle (and most importantly, mindset) accelerates aging and which kind slows the aging process. Jack LaLanne probably had a higher degree of functional longevity than almost any traditional tribe member. Don Gorske will outlive most Eskimos eating only Big Macs, parfaits, and Coca Cola, presumably because “he’s lovin’ it.”

But just because a traditional tribe ate something does not mean that a certain food gets an out-of-jail-free card. Hey, many of them ate shellfish. So shellfish are healthy. Oops, sorry you had an anaphylactic reaction and died eating that healthy food.

We are in a new frontier of human society and it calls for great flexibility with our eating, and a better understanding of the straightforward relationships between food and our physiology. The world is so unique in the history of our species that trying to match an old diet with a new lifestyle and a truly new physiology (hyperinflammatory) is no guarantee, and may create a mighty mismatch. As I’m sure many of you will see if you’ve attended some kind of traditional nutrition conference, the health status of the attendees on a generic “traditional” diet doesn’t appear to be any different than that of the mainstream public. It is not a panacea. It does not appear to be worth the grandiose effort of trying to eat a mythological “perfect diet” built around an unintelligent hodge podge of what traditional peoples around the world ate to go with their specific lifestyle, environment, and epigenetic blueprint.

Speaking of blueprints, like the line uttered by Chong Li at Frank Dux in the movie Bloodsport, I looketh in the direction of Sisson, pointing, and say, “You are next.”  We will have some fun with 80-10-10 raw vegan as well. 



One word summary of traditional diets... IRRELEVANT!

If you’d like some ammunition to make fun of me, read my FREE EBOOK where I am annoyingly fixated on traditional diets and say "Masai" and "Kitavan" about 20 times each.