SOURCE: Lurie I, et al. Antibiotic exposure and the risk for depression, anxiety, or psychosis: A nested case-control study. J Clin Psychiatry 2015;7:1522-1528.

There might be a more important gut-brain connection than we have previously recognized. Animal data indicate that germ-free mice, whose intestinal tract is absent bacteriae, have magnified hypothalamic-pituitary-adrenal responses to stress, which may be normalized by restoration of the intestinal microbiome with probiotics (Bifidobacterium infantis). Similarly, germ-free mice differ in turnover of neurotransmitters associated with mood disorders (e.g., norepinephrine, dopamine, serotonin) from mice with established intestinal bacterial flora.

Since gut flora alteration through antibiotic administration is a commonplace experience for most adults, might such exposures, by altering the intestinal microbiome, also be associated with mood disorders in humans?

Lurie et al performed a case-control study using medical records from a very large database in the United Kingdom inclusive of the interval from 1995-2013. Patients with depression (n = 202,974 with 803,961 age- and sex-matched controls), anxiety (n = 14,570 with 57,862 matched controls), and psychosis (n = 2690 with 10,644 matched controls) were compared for likelihood of having received an antibiotic prescription at least 1 year prior to the recorded mental health diagnosis.

Patients who had received a prescription for penicillin, cephalosporin, or quinolone were more than 20% more likely to incur depression, which increased to 40% more likely if multiple penicillin prescriptions had been issued. Similar odds ratios for anxiety occurred in relation to penicillin and sulfa drugs. Psychosis was not associated with antibiotic administration. Indeed, all antibiotic classes studied demonstrated increased risk for subsequent incident depression.

Of course, it could be that persons with anxiety and depression, even in the pre-morbid state, might be more likely to become ill and receive an antibiotic prescription, nullifying a cause-and-effect relationship. Until the causal relationship between antibiotic administration and mental health is better understood, clinicians could consider adding still another rationale for why we might need to be ever more judicious about the appropriate use of antibiotics.