Infection and Psychosis in Schizophrenia

Last year the daughter of one of my patients called me. "Mom is acting really strange. She's being aggressive, and she thinks my Dad is still alive. I don't think she slept last night. Do you think she needs an increase in her medication?"

Tame Impala: Elephant

My patient was a sweet 70 year old woman with a psychosis-heavy bipolar disorder who could get paranoid from time to time, but was never violent, and had been stable on a low dose of medicine for many years. I told her daughter, "If she didn't fall down and hit her head somehow, I think she has a urinary tract infection (UTI). You should take her in to see her primary care doctor if she'll let you. Otherwise, you might need to take her to the ER."

A few hours later, the daughter called me back, quite amazed. "You were right! Her doctor says she has a bad UTI. How did you diagnose that over the phone?"

I'm sure all my psychiatrist/doctor readers were guessing the outcome right away. UTIs rather famously turn into strange behavior in the elderly, particularly in those with dementia. One time when I was on call in the emergency room, we got a consult for new-onset obsessive compulsive disorder in  77 year old. My fellow resident and I exchanged looks and told the emergency room intern to wait for the results of the urinalysis before we were consulted. 77 year olds don't develop OCD out of the blue without something else medical going on. We were correct�she had a urinary tract infection. The "OCD" resolved with antibiotics. The tricky part for doctors is that these UTIs can occur without any of the usual symptoms we are used to hearing about. No incontinence, fever, or urinary urgency. Or sometimes the patient can't tell us about these symptoms.

So we already know that urinary tract infections can cause pretty weird behavior in vulnerable people. Recently Brian Miller, MD from Georgia Health Sciences University wrote an article in Psychiatric Times about his recent study in the Journal of Clinical Psychiatry: "A Prevalence Study of Urinary Tract Infections in Acute Relapse of Schizophrenia." Not only do I have a subscription to JCP, but my academic access should grant me full access, but on a Sunday morning I was unable to get a copy of the full text because JCP's website is HORRIBLE. In desperation I emailed Dr. Miller, and on Monday morning he very kindly sent me not only a copy of the full text article, but also his letter to the editor in Schizophrenia Research. Thank you!

Schizophrenia is associated with hugely increased mortality, and those afflicted die in increased numbers and earlier from almost every major leading cause of death. Heart disease is most famous (blamed on the increased schizophrenic tendency to smoke and to the effects of the medications), but schizophrenics have an 8-fold increased risk of death by pneumonia. Is it from lack of self-care and not being organized enough to go to the doctor for serious medical symptoms? Maybe. That has been the assumption. But recent studies have shown what is no surprise to followers of Evolutionary Psychiatry. Schizophrenia is not just a brain disease, it is a disease of immune function. Schizophrenics have major abnormalities in levels of inflammatory cytokines, C-reactive protein, and reduced neutrophil activity. Neutrophils are a first-line response to inflammation and are vital to keeping us safe from bacterial infection. 

Despite all these abnormalities, Dr. Miller notes in his paper that there are NO studies of the prevalence of infection at the time of infection of hospitalization for acute illness relapse in patient with schizophrenia. As all clinical psychiatrists will know, schizophrenics can remain relatively stable for many years, then have terrible relapses of psychotic behavior. Often going off medication or substance abuse is blamed (and may well be responsible). But sometimes something else is going on� and it may well be a bacterial infection. Dr. Miller studied healthy controls and some long-term schizophrenics admitted with acute psychotic relapse. He found that those hospitalized with schizophrenia, men and women, were 29 times as likely as controls to have a urinary tract infection. 35% of subjects in the acute relapse group had serologic/urinalysis evidence of a UTI as opposed to 5% of stable outpatient and 3% of controls. 

There are reports of certain antibiotic treatment associate with increased risk of psychosis (cipro and gatifloaxin are known)� is it the antibiotics, or the UTI they were treating? It is well-known that elderly and particularly demented patients are vulnerable to odd behavior caused by urinary tract infections. It is not beyond the realm of possibility that people with schizophrenia are vulnerable to the same pathology. 

The time is coming that schizophrenia is recognized as a full-body immune dysregulation disorder, from the gut to the brain to the neutrophils. At that point are the psychiatrists going to be removed from the picture and the allergists and rheumatologists to step forward? We'll see. 

Read More..

Gut and Brain Again

A long time ago, when I was an intern, I would drive into the hospital for ultra long shifts. Day went into night into the next day. You might be lucky to get one day off in a month. It's illegal now to work interns as much as we were worked, and I understand the sleep science behind the laws. But at the same time, you learn something about yourself and your patients in the long march over a day and a night and a day.

Bono says this song is about a hangover. I used to listen to it on repeat during that sleep-deprived drive into work for those long, long days. In A Little While. I would close my eyes on the elevator in the hospital and hear it playing in my head. Right now I am working a great deal on various projects and of course with my clinical practice. I hope to get a little bit of a break before too long�and have time to do more fun and interesting reading and blogging.

When we are born, we are colonized by the first generation of those eventual 100 trillion bacteria from nearly 1000 differenct species that makes up 90% of the cells of our body. These cells communicate with our brain and likely affect our behavior. The organisms help us to break down complex polysaccharides and they are critical to the normal development of the immune system. A relatively new paper reviews how they might influence anxiety and depression (1).

The mircobiome is influenced by age, diet, stress, metabolism, antibiotics, geography, and genetics. As regards stres reponse, mice lacking a microbiome have an exaggerated hypothalamic-pituitary-adrenal response to stress compared to mice normally colonized. The mircobiome seems to play a role in programming stress response from the very beginning. Stress will also increase intestinal permeability, which gives the bacteria of the microbiome greater access to communicate via inflammation and the enteric nervous system. Microbes can communicate with the human brain via various neurotransmitters, such as GABA, and there is also evidence that different gut bacteria have different effects on serotonin signalling in the central nervous sysem (at least in mice).

When pathogenic bacteria are introduced into the gut of mice, a robust central nervous system response is evident via the vagus nerve, followed by a systemic inflammatory response. Friendlier bacteria (such as lactobacilli) also elicit a central nervous system response, but not the systemic inflammation. Also in mice, certain neurons of the enteric nervous system change how excitable they are (or how easily they signal) depending upon the species of bacteria in the gut. Now repeated in many studies, the infection of mice with pathogenic bacteria increases anxiety-like behavior and treatment with friendly gut bacteria reverses the change in behavior. In some of these studies, changes in the production of nerve fertilizer (so to speak), brain-derived neurotrophic factor, matched the increases and decreases in anxiety-like behavior. The friendly bacteria are associated with greater nerve plasticity and repair, whereas the pathogenic bacteria showed the opposite.

In humans, there are few studies, and none in people diagnosed with clinical anxiety or depression. However, in a double-blind placebo controlled trial of probiotics given for 30 days (2), healthy volunteers who took the probiotic showed significantly less psychological distress than those who didn't. Another three week study showed the healthy volunteers with the most depression-like symptoms had significant improvement on a probiotic while those who took placebo had no benefit (3). There are also positive studies showing probiotics impacting anxiety symptoms in people with Chronic Fatigue Syndrome and undergoing cancer treatment.

Many questions remain that must be further studied. There are differences in how easily the gut microbiome is changed in different life periods, with childhood perhaps showing more amenability to change. In adults it is likely that fecal transplants and the introduction of chronic parasitic infection are the only practical way to permanently affect the microbiome. Childhood exopsure to antibiotics and probiotics may have different consequences than adult exposure to the same.


(2) Messaoudi, M. et al. (2011) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2, 256�261

(3) Benton, D. et al. (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355�361

Read More..

APA Annual Meeting 2013

Many months ago, psychiatrist extraordinairre Drew Ramsey, MD of Columbia University asked if I would be part of a group to present information in a workshop format at the American Psychiatric Association annual meeting in San Francisco. He submitted an abstract, rounded up a reputable mentor on the scientific advisory board and collected not only myself but also Mala Nimalasuriya, MS and Roger McIntyre, MD to present.

Leagues: Spotlight

I must admit I've been a very bad academic up until this point. I keep the tip of my little finger in the academic world by teaching the clinical section of the introduction to psychiatry course at Harvard Medical School and have given a few Grand Rounds and other CME talks around town, but I haven't published or done any research besides serving as a psychiatrist for a project in the first couple years after residency. So for me, the opportunity to present at the largest annual meeting of psychiatrists in the world seemed, well, amazing. I do try for the blog to be honest and based on common sense and evidence and practicality, but at the end of the day, it is just a blog, and there are probably 10,000 new blogs on the Internet every single day.

Writing articles for the blog entertains me, helps me to learn, and is a lot more fun than toning it down for the interminable language of scientific papers, which tend to be interesting yet hideous unless written by the best (such as Gabbard or Rook). I do admire those who do publish, like Dr. McIntyre, whose resume is about 80 times as long as mine.

But I never look a gift horse in the mouth, and if they wanted me to present at the APA, I would help deliver�

Drew began the presentation with a brief overview of some important brain nutrients and the concept of whole foods versus the ubiquitous bastardization of wholesome living food we call "processed food." Drew's example: "I went to the store to buy some ham, and it was advertised as 'gluten-free.' When did gluten get into my ham?" He also reviewed some of the dietary pattern studies and elimination diet studies I've mentioned on my blog from time to time. Drew is both an expert at the various nutrients in whole foods, but also anti-"nutritionism," highlighting the importance of combinations of nutrients and their availability in whole foods that is quite different from the stripped down nutrients replenished with salt, industrial fats, and synthetic vitamins so prevalent in processed foods. Drew is the author of The Happiness Diet and the upcoming 50 Shades of Kale (he did indeed order the kale salad at the Split Bread in San Francisco).  I'm going to review The Happiness Diet soon, once I get a minute�

Maya continued the talk with information from her master's thesis on nutrition, the brain, and brain derived neurotrophic factor (BDNF). BDNF is brain fertilizer that helps with neurogenesis and repair, and good nutrition is associated with goodly amounts of BDNF.

Roger followed up with his vast body of work on obesity and mood disorders, noting the effects of weight loss, obesity, and active mood disorders on particular inflammatory cytokines. He highlights the point that the success I see with some of my folks on a paleo-style diet may be a result from an anti-inflammatory state that comes along with weight loss rather than from any particular diet per se.

I was the closer for the presentation with a very brief overview of the evolutionary medicine hypothesis, its pluses and pitfalls, the commonalities of a paleo-style diet and some evidence (including the evidence on fructose malabsoprtion) linking modern diets to poor mental health. I gave a few case studies and my clinical pearls for helping introduce a whole foods diet to people as part of a holistic model for health care in addition to more traditional therapies. I also discussed the theoretical applications of ketogenic diets in psychiatric disorders, the available evidence (almost nil: all pilot trials or case studies), and advised folks to keep an eye out for more research.

We had a number of questions and interest in the ideas of celiac disease masking as major mental illness, coconut and MCT oil, tofu and the poor performance of so called "modern diets" in the dietary pattern studies and depression, and interesting tracks for research and some practical questions about implementing recommendations. At the end we were approached by a number of psychiatrists wanting more information.

Did I mention our room was completely packed with people sitting in the front and aisles and lined up out the door?

All in all, a great success.

The remainder of the APA was, as always, interesting. 15,000 psychiatrists and the launch of the DSMV meant a continuous Scientology protest outside, plus a number of men with bushy eyebrows and bow ties. I attended a number of lectures, the most notable being a 4 hour seminar on giving better lectures. The APA attracts psychiatrists from all over the world, and I would estimate the number of international attendees at 1/5-1/4 in the lectures I attended.

I happen to be friends with the son of a former president of the APA, and as such was able to finagle my way into the APA Presidential Reception at the Palace hotel, which was great fun. My friend's father and his wife very kindly introduced me to everyone, and I can't express my appreciation enough.

It was also great to hang out with Drew Ramsey; food-minded and sensible psychiatrists are always a pleasure to talk to, crossing fingers we'll be invited to the next APA, and I'm going to get his 50 Shades of Kale to help me cope with the mountains of kale I get from my CSA, which starts up next week.

Read More..

A Bit of Hiatus

Hi there. Yes, it has been a while. I am spending several hours each day working on the book, so other writing has taken a back seat for the moment. In addition, I am preparing for the upcoming American Psychiatric Association Annual Meeting in San Francisco, where I will be presenting as part of a group on food and the brain (on Sunday afternoon, before the Clinton speech, for anyone who will be there). My next talk after that will be in Arlington, VA, as I have graciously been asked to be a (far less glamorous and much shorter) speaking substitute for the Melissa half of Whole9Life for the summer of Melissa's maternity leave. You can get tickets for the talk here. I'll be adding a bit on the psychology of change and sleep cycles to the general Whole9 information.

Sometime in the next week or so I will have a new (or new-ish) post on Psychology Today. And you never know what will happen if a white-hot paper comes to my attention.

In the meantime, have a lovely spring. Keep checking back, and as always I'm still far too talkative on twitter.

Read More..

Marathon Monday

I've always worked on Marathon Monday until this year, when we went to California to visit my sister for the week. Otherwise, since my oldest is now in school and had the day off, we may well have been downtown to see the festivities. For four years I lived about a half mile from where the bombings took place. I've walked down Boylston Street hundreds of times.

Two things folks who have not spent time in Boston may not understand about the events in Boston and Watertown this week: Marathon Monday, Patriot's Day, is a family event. I personally knew hundreds of people who went down to the race, because nearly everyone seems to go. My niece and nephew had watched a bit just down the block, though they had left by the time of the bombing. My sister-in-law knew a woman, a nurse, and her new husband who both lost limbs from the bomb, but so far I've not heard from other friends, family, or patients who were hurt. The "could have been" is sobering.

The second thing to understand is that Boston proper is a very small city. One could walk across it in a few hours. It is just a bit of a walk across the river to Cambridge, more of a hike over to Watertown. Closing down the city to do a confined manhunt in Watertown might seem unimaginable in Manhattan or Dallas or Los Angeles, but it is not so terribly far-fetched in Boston.

I mostly know the medical community, and some people in the law enforcement community. Atul Gawande wrote a good post for The New Yorker online about why so many survived the initial blast despite critical injuries. Today there are more than 50 people still hospitalized. And of course the five who died (including the MIT officer who was shot by the alleged bombers on Thursday night/Friday morning and the older bombing suspect himself). We will go back to work tomorrow and see how people are handling what happened, though I was on call for the practice and spoke with a few people who were very shaken up, particularly on Friday.

It was a good week to have been away, but I am glad to be home. My family is safe and sound, and it is so terrible that so many families were maimed and wounded this week. Thank you to those who reached out to me via social media and email, concerned about us.

Source

Read More..

Sunlight, ADHD, and Current Events

First off, a brand new post is up on Psychology Today (one never before seen on this blog):

Sunlight and ADHD

Secondly, the blog has been a bit quiet of late because I am busy trying to get some real work done on the book. The deadline for a solid first draft is fast approaching.

In light of some shake-up in the blogosphere and the recent paleo debunking fad, I do plan a little post about what I think of the "paleo-style" diet (though long-time readers probably know my opinion already).

Also, for any of you who speak Polish, many of my articles have been translated�here is the link from Joanna Satula-McGirr: http://mojapsychologia.pl/eksperci/13,emily_deans_m_d/

Stay tuned!

Read More..

PaleoFx13 and BA Training

Last weekend I went down to Austin for the PaleoFx13 conference. While I enjoyed PaleoFx12, I had a bit of trepidation at the idea of going back, mostly because the science talks were exceptionally fringe. However, I really enjoyed the people, and since I�m originally from Austin, it�s a nice excuse to get down for a few days and see my family and old friends and escape the horrendous early spring in the Northeast.

Muse: Panic Station (really digging the 21st century Stevie Wonder vibe of this song)

PaleoFx13 was a blast. The venue at the Palmer event center was terrific. Keith and Michelle Norris and all their help (including Corben Thomas among others) organized things very well, and the focus was drawn away from the sketchy science of yesteryear and more towards functional fitness and practical applications. For all the recent acrimony and problems in the paleoblogosphere, PaleoFx manages to make ancestral health a lot of fun. And we definitely needed the fun.

My contribution as a presenter was not fringe at all, but rather the evidenced-based application of behavior theory and stages of change and motivational interviewing on lifestyle changes in general. I use these techniques pretty much every day in my clinical practice in coping with addiction and other lifestyle changes, so it was both straightforward for me and rewarding. Several physicians came up to me after the presentation and spoke to me about their need to really tailor interventions to the particular stage of change of the patient to reduce frustration and prevent wasted energy. My friend, Jacob Egbert DO used the second half of our presentation to talk about his interventions in the gym, his success stories, and the idea of a gym (or any community) as a primary care center for wellness and prevention of chronic disease. He has struggled a great deal with the paradigm of modern medicine and the push for more procedures, more billing, and less holistic care.

I spent a lot of time with my online coach, Clifton Harski of BA training and his amazing girlfriend, Amy. She is a gymnast and he a kinesiology major and former MovNat master trainer along with a ton of experience with other forms of functional fitness. 

The term �functional� merely refers to full body, useful movement, such as getting up from the floor or climbing trees or Olympic weightlifting. I�ve been doing a program designed by Clif for about two months, and my general strength and movement has increased a great deal, even after two years of CrossFit. His BA training �Bootycamp� uses a lot of bodyweight movement and kettlebells to increase lower body stength. It�s high volume and intense, and beneficial, though he backed off and lightened my workouts when I was having a stressful week. Despite an injured shoulder, I�ve been able to do some legit chin-ups since I started his program. Between that and the heavy deadlifts, I can draw a lot of eyes in the globogym.

In person training (with an excellent trainer)  is always best, but with my time constraints and boredom with the standard fare (and the fact that I am just a psychiatrist who can do chin-ups rather than some sort of athlete), the online training keeps things interesting as well as challenges me in a way that local trainers probably wouldn�t. In person, Clif helped me perfect my two-kettlebell swing while Amy helped me achieve the one-armed handstand (against the wall!). Clif, like many of the folks I admired at PaleoFx loves perfecting human movement. It turns out I have an issue with my hip adductors, which my CrossFit trainer had noticed, and kept ordering me to keep my knees out on squats, but that wasn�t enough to fix the problem. 

Clif�s programming of one-legged deadlifts helped me to isolate the problem and start to work on it. He also respected the limitations of my shoulder and programmed specific strength exercises with that in mind. He is thoughtful about movement and functional training, but also recognizes that fitness should not be so deadly serious that we can�t enjoy it (just like paleo food�fun healthy delicious food as opposed to quinoa and textured soy protein? Sign me up!)

At PaleoFx I was fortunate enough to hang out with all the folks who goof off and do stupid human tricks between conference sessions, including Amy, Skyler Tanner (my favorite efficient exercise trainer) and Jacob Egbert. (Photo taken from A Jolly's twitter stream.)

I won�t be able to post before and after pictures of my bootycamp derriere, but rest assured I�m stronger and more shapely after the introduction to Clifton�s program. His brilliant tagline is �turn that applesauce into apples.� I�m going to hire him to give me some extra workouts in the future along with 2X  a week CrossFit training (nothing like the social crew at CrossFit to keep me motivated and coming back for more early morning gym time). 

Hopefully I will be able to attend PaleoFx14 and beyond! Life is becoming incredibly busy�today I presented at Psychiatry Grand Rounds at a hospital in Cambridge and it was very well received. Last week I presented at UT Austin, and flubbed the talk a bit as I am used to presenting a lower-level talk, or to clinical medical audiences. All the criticism and experience is very welcome. My wish is that a medical student and his or her eager mentor will latch hold of the idea of studying fructose malabsorption and depression. And if it is fecal transplants and depression instead, or magnesium and depression, or whatever, I will be a happy camper. 

Read More..