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Tuesday, June 18, 2013

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?"


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. 

23 comments:

  1. Amazing. In "The madness of Adam and Eve" there are stories of chronic schizophrenia remitting temporarily during fevers. This may be another way in which the immune system can resolve these imbalances.

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  2. this rings so true. I work in a big hospital with multiple ICU's. UTI def increases delerium in older patients. More psych pts end up in the ICU with UTI too.

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  3. i can't help but think of the hbo series "girls."

    the main character gets a uti. shortly after all her old ocd symptoms come back.

    at the time, i thought the two may be related-- although this connection is never acknowledged on the show. so many mood disorders seem to involve the immune system (pandas, ibs)

    i hope you write more about this in the future!

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  4. Exactly. My wife (Chinese) just got back from Taiwan where her 85 yo mother exhibited some extreme behavior - such as threatening to jump off the roof. My wife took her to an MD and it was determined that she was suffering from UTI. She also took her to a psychiatrist because of her behavior. The psychiatrist prescribed Zoloft.
    I showed this to my wife and she was astounded.

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    1. Sometimes the elderly can develop a new and dangerous psychotic depression with no UTI involved, but I recommend waiting for the urine to clear before treating with antidepressant medicine… what is fascinating to me is that I can't imagine any training program for psychiatry neglecting the basics such as UTIs and delirium and bizarre behavior in the elderly. It is so common I would hardly think to blog about it. The schizophrenia connection is extraordinary and unexpected.

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    2. I assume you have seen the recent info on chronic back pain being up to 40% related to infection. I wonder if there isn't more to the whole pleomorphism / Dechamp theory. http://www.healingnaturallybybee.com/articles/germ12.php#a2

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  5. And once a bipolar depression disappeared completely for me during a pneumonia (and stayed away when I had recovered).

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  6. Are the UTIs caused by poor hygiene? Or what?

    The demented mother-in-law of one of my patients was also exhibiting increasingly disordered behaviour last summer and sure enough it was UTI.

    Although it's not my expertise except through personal experience, conversations do come up and I always recommend that people wash and not just wipe after a BM. Oh and it's incredible how many women don't know they shouldn't wipe feces forwards! I figure if people get into the right habits early in life, when they get older, the better ways will become habitual. Nobody should have brown streaks in their underwear. Patients take it on as a new habit and are grateful. (Why don't people wash after a bowel movement if they are at home? Why don't other doctors instruct them? It might save a lot of trouble.)

    Also, after sexual intercourse, doesn't matter how sleepy, get up and go pee.

    I'm the dentist. I just chuckle that sometimes I'm seemingly responsible for the digestive tract from one end to the other.

    Question: Lithium causes goitre? Patient has chronic hairloss and swelling of thyroid. Her doctor think it's fine. Maybe she's afraid the patient will get manic if given a low dose thyroxine?

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  7. I do wonder? I'm not knowledgeable enough to understand all that I read in most health blogs. I was recently diagnosed with a B12 deficiency after being symptomatic for over 10 years. It doesn't get checked or treated because of insurance of coding problems (my opinion). Anyway,in my research on B12, mental problems and bladder infections are common symptoms of B12 deficiency; brain shrinkage and nerve damage. Could B12 deficiency be the connection? B12 deficiency is inexpensive to test and treat. Also, taking Niacin makes me psychotic with sudden rage could there be connection with B12?

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  8. Typo in recognized, final paragraph. Just FYI.

    Very interesting piece. My grandmother always gets more confused etc when she has a UTI.

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  9. This makes me wonder about autism and GF/CF diets. I've never been big on the peptide explanation of why it works. Until reading this post I figured GF/CF effectiveness was a relief of digestive problems that were exacerbated by sensory integration issues.

    We have now gone from the brain gut axis to the brain bladder axis.

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  10. Emily, what do you have to say on supossed metabolic conditions like pyroluria? Orthomolecular practicioners say it may be of great importance to mentally sick people, and it was initially studied as related to shizophrenia. I do wonder about its veracity, both related an unrelated to schizophrenia. Also, do you think thyroid problems can be directly related to it?

    In line with the last question, but a bit unrelated to the topic; when do you think it is worth trying thyroid drugs in a mental health patient? I haven't read all your posts, so sorry if this is redundant.

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  11. Emily, what do you have to say on supossed metabolic conditions like pyroluria? Orthomolecular practicioners say it may be of great importance to mentally sick people, and it was initially studied as related to shizophrenia. It's supossed to affect inmunity too, I think, I do wonder about its veracity, both related an unrelated to schizophrenia. Also, do you think thyroid problems can be directly related to shizophrenia?

    In line with the last question, but a bit unrelated to the topic; when do you think it is worth trying thyroid drugs in a mental health patient? I haven't read all your posts, so sorry if this is redundant.

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  12. I wonder, why the phenomenon is typical for elderly population only? What about younger people? How much younger then 65 a person should be in order to avoid infection-related mental problems?

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    1. It's more common in demented folks, I think brain-injured folks as well whatever age. Not sure if it is more common in autism? Would have to check on that one. Older people can also have significant infections without having the typical symptoms of fever and pain on urination.

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    2. I remember reading in the Dr.Bernstein's book that almost always , when his patients had an unexplained elevated blood sugar level, it was due to some undetected infection, especially dental one (if I remember all details correctly). What if the hard to control BS the common denominator here?It is safe to assume that the elderly have more problems here. I am a 52 yo person who has to eat a LC diet in order to live a healthy life. In my case several things get better or worse in a claster - there are allergies, migraines, mood problems, nfections including urinary truct ones, weight.

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  13. This is really interesting! Although I am a surgeon, psychiatry fascinated me, and I did all of my elective rotations there. Also my aunt is diagnosed with paranoid schizophrenia and being only a little younger than her, I have watched this terrible condition affect the entire family.

    Any improvements in the treatment for this is a wonderful thing!

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  14. Seems like another study looking at a high prevalence condition and suggesting there is a correlation to psychopathology (like vitamin D studies). The authors note that they omitted some of the basics here like checking for a fever and symptoms. There are several other conditions that can result in low numbers of WBCs in the urine that are not infectious processes. Having spent 22 years screening patients for acute admissions I don't think that pyuria per se will correlate with much in young folks with acute psychosis.

    Two of the author's here have an interesting article in Focus that provides a lot more detail of the immune effects that may lead to relapse in schizophrenia:

    http://focus.psychiatryonline.org/article.aspx?articleID=1201001

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  15. I always like reading your blog, and I was pleasantly surprised to hear some Tame Impala!

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  16. I learned this fact as a paramedic. When you arrive at the dementia unit to hear from nursing staff that a patient's dementia has become acutely more pronounced within a day or two, 9/10's it's a UTI (sometimes a unrecognized CVA, but that's another story).

    I'm curious to whether the studies that have led to see these immunity abnormalities used patients who were not on antipsychotics.

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  17. Very interesting article.
    I am a microscopist and have viewed MANY microbes in the blood of schizo's (using phase contrast, 1 000X oil). My son has schizophrenia and suffered from concurrent multiple infections since childhood.
    Since using a course of antibiotics and extended herbal antibiotics, he was able to reduce medication over the period of a year to NIL. At the starting point of the 'treatment' he was deemed 'treatment resistant' and we were told to institutionalize him (after struggling for almost five years to stabilize him). Now he has no positive symptoms whatsoever (and they were really bad) and is slowly improving with neg symptoms. But he smiles at appropriate times now, sleeps well with no meds, takes care of personal hygiene with no reminding needed. He also does not avoid us as he used to, but joins in all the family activities.
    The infectious hypothesis needs investigation at greater levels.
    I have also seen the same microorganisms in other schizophrenic patients. But no one is interested in this at all. So many continue to suffer.

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  18. Thank you for this article and Dr. Millers article on the same subject. My wife is 47 years old and is currently on a involuntary hold at a mental hospital after a psychotic episode. I have known her for 30 years and she is the most stable woman that I have ever known and we have had the best marriage of anyone that I know. This is her third hospitalization in the past 9 months for the same psychotic issues. She has had a lot of stress in her life including my 18 year battle with chronic illness. The past 2 episodes they determined early that she had a severe UTI, and they began to give her strong antibiotics and within a couple days she was greatly improved. In both of those cases she was released after only 7 days of treatment. I have had 6 psychiatrists at three different locations all tell me that they don't know why these episodes happened, but one thing they all swore to, was that my wife had no mental illness. The months between episodes she seemed to be 100% her old self, and then it would all happen again. I just found out that she also has a bad UTI this time. The doctors seem to think it isn't related and they told me that UTI's are usually only a key in elderly patients. I can't believe this, if it can happen in the elderly it can happen to anyone given the right conditions. But how do I convince the doctors to explore this possibility more. The last 2 events involved her getting naked and walking outside our home going to see God. I believe this could be from her feeling very hot inside due to the infection. I am terrified that they are simply going to release her once she is stable and I will have to live everyday wondering if it is going to happen again or not. If anyone can help me, or the doctors treating my wife please contact me at walknmiracle@triad.rr.com . Please pray for my wife and my family. Thank you.
    Kevin

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    1. I just want to share my experience - after 45 many things in my health got abraptly worse despite my life-lond healthy life-style habbits. Among my problem were migrains, asthma, frequent infections, especially yeast and UTI, weight gaine. In order to manage migraines, I gave ketogenic diet a try, end everything else got better. I still have migraines (much weaker and less frequent), but all infections just disappeared since November 2007. It looks for me, many poeople experience multiple health problem to age-related changes in their metabolism. Addressing diet leds to the better regulation of body systems.

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