Flu funk may have ties to depression

VANDERBILT (US) — The bad mood that often comes with the flu may be triggered by the same immune system mechanism linked to depression.

Scientists were able to produce “despair-like” behavior in mice by activating the immune system. Details are reported in the journal Neuropsychopharmacology.

“Many people exhibit signs of lethargy and depressed mood during flu-like illnesses,” says Randy Blakely, a professor of pharmacology and psychiatry at Vanderbilt University. “Generally these have been treated as just a consequence of being physically ill, but we think there is likely to be something more brain-centric at work here.”

Blakely and colleagues previously reported that inflammatory cytokines can enhance the activity of the serotonin transporter (SERT), which regulates the supply of the neurotransmitter serotonin in the synapse, or gap between nerve cells.


Prozac (shown as purple discs) increases the amount of serotonin in the synapse by blocking serotonin reuptake by the serotonin transporter. (Credit: Randy Blakely, Vanderbilt)

Elevations in SERT activity remove serotonin from brain synapses at an enhanced rate and, based on studies in animal models and humans, would be predicted to increase the risk for mood and anxiety disorders. Indeed, a class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs)—such as Prozac and Zoloft—work by blocking the ability of SERT to eliminate serotonin.

In the current study in mice, the researchers triggered pro-inflammatory cytokine production. Within 30 to 60 minutes, SERT was activated in the brain and the animals displayed despair-like behavior.

Remarkably, this behavior was not observed when cytokine production was triggered in mice lacking the SERT gene. Similarly, a drug that blocks inflammatory molecule signaling also prevented stimulation of SERT and the despair behavior. “It’s as if these inflammatory molecules are an ‘anti-Prozac,'” Blakely says.

In their paper, the researchers cautioned that “we do not presume that changes in SERT activity alone are sufficient to induce the full spectrum of depression traits, nor that our animal model can reproduce all the elements of a complex neuropsychiatric disorder.”

“Nonetheless, we were able to identify a mechanism that may be a engaged, even without inflammation, to impact risk for depressive illness,” Blakely says.

Identifying genetic variations in the SERT activation pathway, for example, might suggest additional sources of genetic risk for depression. “Our work suggests that novel therapies targeting inflammation-linked pathways may be of use in the treatment of mood disorders,” he adds.

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