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Never Quite as It Seems: An Apparently Chance Association May Explain a Lot About Schizophrenia

Never Quite as It Seems: An Apparently Chance Association May Explain a Lot About Schizophrenia

Shallow men believe in luck or in circumstance. Strong men believe in cause and effect.

—Ralph Waldo Emerson

How frequently do you find yourself prescribing antibiotics for inpatients with schizophrenia and related psychotic disorders during hospitalization? While working as a psychiatrist on our acute care inpatient unit, I asked myself this question and came up with an (anecdotal) answer of, “For somewhere between 1 of 5 and 1 of 3 patients.”

I had treated patients with comorbid urinary tract infections (UTIs), cellulitis, and occasionally, upper respiratory tract infections (URIs). The more I thought about my answer, I was struck by 2 observations: (1) I have diagnosed schizophrenia and comorbid UTI in males, but the combination is more common in females; and (2) some patients with comorbid infections had relapsed despite good adherence with medications and in the absence of other specific psychosocial stressors. For these patients, psychosis often improved following antibiotic treatment for the infection, often without need for changes in psychotropic medications.

In my clinical training, I had learned to screen vigilantly for UTIs in geriatric patients with psychosis in the context of dementia or delirium. But it turns out that my simple clinical observation is backed up by quite an intriguing literature regarding infections and schizophrenia.

Prenatal maternal viral and bacterial infections1 and childhood viral encephalitis2 are risk factors for psychotic disorders. Infection with Toxoplasma gondii is highly prevalent in patients with first-episode psychosis.3 In patients with schizophrenia, there is also an increased prevalence of HIV infection and infectious hepatitis.4 Importantly, schizophrenia is also associated with increased mortality from all infectious diseases, including pneumonia and influenza.5

Our research team explored whether the association between UTI and acute psychosis extends to patients with primary psychotic disorders. Even with my clinical experience of treating comorbid UTIs on the acute care inpatient unit, the results were striking. In a sample of 57 acutely relapsed inpatients with DSM-IV schizophrenia, 35% of the patients (38% of females and 28% of males) had a UTI on admission, detected by urinalysis and urine microscopy.6 After controlling for effects of gender and smoking status, our patients with schizophrenia were almost 29 times more likely to have a UTI than controls. By contrast, there was no association with UTI between a sample of 40 stable out­patients with schizophrenia and 39 controls. Furthermore, only 40% of the UTIs in acutely relapsed inpatients in our study were recognized and treated with antibiotics during hospitalization.

For clinicians, this association raises the possibility of infections as a potentially modifiable risk factor for relapse in schizophrenia. Acute psychotic relapse is common and relapse prevention represents an important treatment issue in schizophrenia. Illness relapse is associated with adverse outcomes, including increased treatment-resistant symptoms, cognitive decline, and functional disability. Given the myriad of associations between schizophrenia and infections, this relationship appears to be more than just a “chance” finding, and it may be relevant to the pathophysiology of illness relapse. Our findings also highlight the potential importance of monitoring for comorbid infections in acute inpatients with schizophrenia, because fewer than half of the UTIs in our study were recognized and treated during hospitalization. Untreated infections pose an increased risk of morbidity and potentially increase the duration of hospital stay.

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