While the risk for bipolar disorder may be largely driven by genetic variables, these cannot help predict the episodic variations of the disorder. Both immune dysfunction and bacterial infections have been implicated in the development of psychiatric disorders, and previous research found increased immune activation in participants during manic episodes.1-2 “Alterations in the immune system are thus plausible candidates for the episodic changes in behavior [that] are associated with mania,” wrote the authors of a new study published in Bipolar Disorders.3
Researchers at Johns Hopkins School of Medicine and Sheppard Pratt Health System in Baltimore, Maryland, examined rates of antibiotic use in patients with bipolar disorder, schizophrenia, and major depressive disorder, as well as in a control group of patients without a psychiatric diagnosis. The group of patients with a psychiatric disorder included those who were admitted to a day hospital program or an inpatient unit, and data were collected at the time of intake between 1999 and 2016. A prescription for antibiotic medication was considered an indicator of bacterial infection.
The sample contained 1157 participants (59.2% female), including 555 controls and patients with the following diagnoses: acute mania (n=234); bipolar depression (n=101); major depressive disorder (n=70); and schizophrenia (n=197). The findings show that while only 1.1% of control participants were taking antibiotics at intake, the rate was 7.7% among patients experiencing a manic episode. Rates of use in the other patient groups were 3.1% for schizophrenia, 4.0% for bipolar depression, and 2.9% for major depression. Infected areas included the urinary tract (the most common site and occurring solely in women in this sample), respiratory tract, skin, soft tissue, and mouth.
After using logistical regression to adjust for covariates such as age, gender, race, education, and smoking, the authors found significantly higher odds of antibiotic use in patients with mania vs the control group (adjusted odds ratio [OR]=5.5, 95% confidence interval [CI]: 2.2-14.1; P<.0002). Though other patient groups had increased ORs of antibiotic use, they were not statistically different from the ORs of the control group.
The total rate of antibiotic use in psychiatric patients was higher than that in control participants (adjusted OR=3.7, 95% CI: 1.5-9.2; P=.004), and there was no difference found between inpatients vs participants in a day hospital program. Among the specific subset of patients with acute mania, however, antibiotic use was greater in participants who were inpatients vs those who were day patients (adjusted OR=6.1, 95% CI: 2.4-15.8; P<.05).
There are several potential mechanisms linking acute mania with antibiotic use, including an infection-triggered immune response that leads to mania, as well as impaired immune protection and thus elevated rates of bacterial infections in people with mania. There may also be implications for altered gut microbiota, although that would not appear to apply in this case as the medication administration took place over a short period of time.
“The control of bacterial infections in individuals with susceptibility to mania and other acute psychiatric conditions might result in the prevention of acute episodes and a marked improvement in their health and well-being,” the authors concluded.
1. Becking K, Boschloo L, Vogelzangs N, et al. The association between immune activation and manic symptoms in patients with a depressive disorder. Transl Psychiatry. 2013;3(10):e314.
2. Panaccione I, Spalletta G, Sani G. Neuroinflammation and excitatory symptoms in bipolar disorder. Neuroimmunol Neuroinflammation. 2015;2:215-227. DOI:10.4103/2347-8659.167304.
3. Yolken R, Adamos M, Katsafanas E, et al. Individuals hospitalized with acute mania have increased exposure to antimicrobial medications. Bipolar Disorders. 2016;00:1-6. doi: 10.1111/bdi.12416.