Novel influenza A (H1N1) advanced and receded in the United States this past spring, but no one in the public health community expects it to stay away. Whether the flu formerly known as swine will return this fall and winter as a mild breeze or a storm of infection is unknown at press time.

Flu is usually not the concern of psychiatrists (unless they catch it themselves), but some aspects of last spring's mini-pandemic have raised some concerns in the disaster mental health community.

These include not only neuropsychiatric effects of the disease or the medications used to treat it, but the community mental health issues that follow any major disaster (see Flu Outbreak Could Lead to Community Stress).

According to the Centers for Disease Control and Prevention (CDC)," seizures, encephalitis, encephalopathy, Reye's syndrome, and other neurologic disorders" and "acute cognitive and behavioral problems" have been seen in children with seasonal flu. In July the agency reported on four cases in Dallas of neurologic complications in children and adolescents with confirmed H1N1 flu. Those patients represented about 1 percent of the H1N1 cases seen at the hospitals reporting. At various times, one or more of these patients had seizures, were confused, and had difficulty responding to questions. All were hospitalized, treated, and released without long-term mental complications.

"Clinicians should consider influenza-associated encephalopathy in the differential diagnosis of children with [influenza-like illness] and seizures or mental status changes," wrote the CDC in the July 24 issue of Morbidity and Mortality Weekly Report. Such symptoms are manageable in normal caseloads but would presumably appear in greater absolute numbers if tens of thousands of people came down with the flu in one city.

Treatment represents another potential area of concern. The CDC recommends two neuraminidase inhibitors for the antiviral treatment and prophylaxis of H1N1 influenza: zanamivir (Relenza) and oseltamivir (Tamiflu). Recent prophylactic trials in Britain of the latter produced reports of side effects in 21 percent to 33 percent of participants, mostly gastrointestinal or headache, but the small number of participants and methodological problems limit the trials' usefulness.

Occasional reports of "bizarre behavior" after taking these drugs exist, but those effects may be attributable to the illness as much as to the medication. Early reports from Japan of increased suicides among young people taking oseltamivir were not confirmed after an FDA review, which said the events may have been related to high levels of flu-induced encephalitis there. A report last April from the drug's manufacturer (Hoffmann-La Roche) said "no increase in the incidence of claims-based neuropsychiatric events was detected" in users of the drug compared with those not taking antivirals.

Nonpharmaceutical interventions could play a role in holding down infection rates but might produce their own problems. "Social distancing"—closing schools and businesses, staying home from work when sick, and canceling concerts, sports events, and church services—has proven effective in past epidemics but might be hard to continue for more than short stretches of time.

"[M]aintaining the strict confinement of children during a pandemic would raise significant problems for many families and may cause psychosocial stress to children and adolescents," says the U.S. government flu Web site. "These considerations must be weighed against the severity of a given pandemic virus to the community at large and to children in particular."

In the worst case, if schools and child care centers were closed, workplace absenteeism could rise and incomes fall as parents stayed home to look after their children. Economic disruption could become severe. Families with members infected with the flu might be shunned by neighbors. Combined with high mortality rates, all of this would inevitably raise stress levels, or worse, as often occurs after floods and earthquakes.

Another problem might not show up for decades.

Last spring, pregnant women appeared to be at higher risk for severe complications of H1N1 flu, including death, so the CDC placed them at the top of its vaccine priority list.

Research looking at health records from the 1950s and 1960s has found that influenza infection in pregnant women is associated with increased risk of schizophrenia in their offspring. The spring 2009 outbreak struck people under the age of 25 twice as frequently as older people, reversing the seasonal flu pattern and making women of child-bearing age more vulnerable.

The H1N1 virus has some elements in its viral coat similar to that of strains circulating half a century ago, said Alan Brown of Columbia University, who has studied this question extensively. However, its viral makeup may not make much difference.

"Based on our data, the effect on the risk of schizophrenia is probably due not to the flu itself but to immune response, especially the cytokine response produced by activated T-cells," said Brown in an interview. "Infection is associated with a huge cytokine response."

Would the immune response generated by a flu vaccine cause the same problem?

"The evidence is that the cytokine response to the flu shot is far less than that from infection," said Brown. "Influenza is a greater danger when weighing the risks against the benefits."

Brown would like to see the CDC extend its vaccine recommendation to all women of childbearing age.

However, much uncertainty remains because no one has studied the effects of flu vaccine on birth outcome to see the effects of the cytokine response on the fetus, he said.

Finally, a major outbreak might also place enormous strain on health care workers and first responders, if the outbreak of severe acute respiratory syndrome (SARS) in Toronto in 2003 offers any lesson.

There, the mysteries accompanying an unknown pathogen and route of transmission, along with a high fatality rate, raised stress levels in hospital employees, reported Robert Maunder, M.D., an associate professor of psychiatry at the Mount Sinai Hospital in Toronto, in 2004 in the Philosophical Transactions of the Royal Society of London (B).

"[T]he SARS outbreak turned the modern world of health care on its head in Toronto, in the sense that health care workers were seen as victims and vectors of disease rather than healers, and hospitals were seen as contaminated areas rather than places fostering health," wrote Maunder.

Besides worrying about infection risk to themselves, their families, and coworkers, health workers had to deal with the isolation enforced by quarantine procedures. Access to hospitals was restricted, handshaking was forbidden, and protective gear made everyone anonymous without repeated introductions. Staff who followed orders and avoided colleagues reported greater stress, according to a post-outbreak survey. Collectively, this social isolation took its toll on workers, said Maunder.

Novel influenza A (H1N1) may return as a modest surge in the winter's usual flu cases or it may roar back like wildfire across a dry prairie, but anyone involved in caring for patients must be prepared for any of its eventualities.

More information is posted at the CDC's flu Web site at<www.flu.gov/plan/community/commitigation.html#I>.▪