Every psychological disorder, including depression, has some behavioral components.

Depressed children often lack energy and enthusiasm. They become withdrawn, irritable and sulky. They may feel sad, anxious and restless. They may have problems in school, and frequently lose interest in activities they once enjoyed.

Some parents might think that medication is the solution for depression-related problem behaviors. In fact, that’s not the case. The Food and Drug Administration hasn’t approved any drugs solely for the treatment of “behavior problems.” When FDA approves a drug for depression—whether for adults or children—it’s to treat the illness, not the behavior associated with it.

“There are multiple parts to mental illness, and the symptoms are usually what drug companies study and what parents worry about. But it’s rare for us at FDA to target just one part of the illness,” says Mitchell Mathis, M.D., a psychiatrist who is the Director of FDA’s Division of Psychiatry Products.

Depression Is Treatable

The first step to treating depression is to get a professional diagnosis; most children who are moody, grouchy or feel that they are misunderstood are not depressed and don’t need any drugs.

Only about 11 percent of adolescents have a depressive disorder by age 18, according to the National Institute of Mental Health (NIMH). Before puberty, girls and boys have the same incidence of depression. After adolescence, girls are twice as likely to have depression as boys. The trend continues until after menopause. “That’s a clue that depression might be hormonal, but so far, scientists haven’t found out exactly how hormones affect the brain,” says child and adolescent psychiatrist Tiffany R. Farchione, M.D., the Acting Deputy Director of FDA’s Division of Psychiatry Products.

It’s hard to tell if a child is depressed or going through a difficult time because the signs and symptoms of depression change as children grow and their brains develop. Also, it can take time to get a correct diagnosis because doctors might be getting just a snapshot of what’s going on with the young patient.

“In psychiatry, it’s easier to take care of adults because you have a lifetime of patient experience to draw from, and patterns are more obvious” says Mathis. “With kids, you don’t have that information. Because we don’t like to label kids with lifelong disorders, we first look for any other reason for those symptoms. And if we diagnose depression, we assess the severity before treating the patient with medications.”

back to top

Getting the Proper Care

The second step is to decide on a treatment course, which depends on the severity of the illness and its impact on the child’s life. Treatments for depression often include psychotherapy and medication. FDA has approved two drugs—fluoxetine (Prozac) and escitalopram (Lexapro)—to treat depression in children. Prozac is approved for ages 8 and older; Lexapro for kids 12 and older.

“We need more pediatric studies because many antidepressants approved for adults have not been proven to work in kids,” Farchione says. “When we find a treatment that has been shown to work in kids, we’re encouraged because that drug can have a big impact on a child who doesn’t have many medication treatment options.”

FDA requires that all antidepressants include a boxed warning about the increased risks of suicidal thinking and behavior in children, adolescents and young adults up to age 24. “All of these medicines work in the brain and the central nervous system, so there are risks. Patients and their doctors have to weigh those risks against the benefits,” Mathis says.

Depression can lead to suicide. Children who take antidepressants might have more suicidal thoughts, which is why the labeling includes a boxed warning on all antidepressants. But the boxed warning does not say not to treat children, just to be aware of, and to monitor them for, signs of suicidality.

“A lot of kids respond very well to drugs. Oftentimes, young people can stop taking the medication after a period of stability, because some of these illnesses are not a chronic disorder like a major depression,” Mathis adds. “There are many things that help young psychiatric patients get better, and drugs are just one of them.”

It’s important that patients and their doctors work together to taper off the medications. Abruptly stopping a treatment without gradually reducing the dose might lead to problems, such as mood disturbance, agitation and irritability.

Depression in children shouldn’t be left untreated. Untreated acute depression may get better on its own, but it relapses and the patient is not cured. Real improvement can take six months or more, and may not be complete without treatment. And the earlier the treatment starts, the better the outcome.

“Kids just don’t have time to leave their depression untreated,” Farchione says. “The social and educational consequences of a lengthy recovery are huge. They could fail a grade. They could lose all of their friends.”

Medications help patients recover sooner and more completely.

Every year, some unlucky people get the flu even though they’ve had their seasonal shot. One reason, according to a new study, might be their gut bacteria. Researchers have shown that, at least in mice, a strong immune response to the flu vaccine relies in part on signals from intestinal microbes. The findings could help explain variation in the response to the vaccine and suggest ways to maximize its effectiveness.

The microbes that inhabit our bodies—collectively known as the microbiome—may influence everything from obesity risk to food allergies. Recent studies have also shown that resident microbes affect how our immune system responds to infection. For example, mice with depleted microbiomes appear to be more susceptible to the flu. But it wasn’t clear what role the microbiome plays in the response to vaccines.

The new evidence came out of a curious observation that researchers revealed in a 2011 paper. Bali Pulendran, an immunologist at Emory University in Atlanta, and colleagues were looking for genetic signatures in the blood of people injected with the trivalent inactivated influenza vaccine—a mixture of three flu strains. They wanted to know whether the expression of specific genes in the immune system’s white blood cells correlated with the amount of vaccine—specific antibodies in the blood—which indicates how strongly a person’s immune system responds to the shot, and how much protection that person will gain against future infections. In a long list of genes associated with strong vaccine response, the researchers found an unexpected one: the gene that codes for a protein called toll-like receptor 5 (TLR5).

“We thought this must just be a coincidence,” Pulendran says. TLR5 is a sensor of flagellin, a protein that makes up the appendages of bacteria. Why would a receptor that interacts with bacteria in the gut have anything to do with the body’s response to a virus injected into muscle? Maybe, the group thought, B cells—the white blood cells that produce antibodies—receive a signal from bacteria that boosts their activity.

To explore that possibility, the researchers designed a new study using mice. They gave the flu vaccine to three different groups: mice genetically engineered to lack the gene for TLR5, germ-free mice with no microorganisms in their bodies, and mice that had spent 4 weeks drinking water laced with antibiotics to obliterate most of their microbiome.

Seven days after vaccination, all three groups showed significantly reduced concentrations of vaccine-specific antibodies in their blood—up to an eightfold reduction compared with vaccinated control mice, the group reports online today in Immunity. The reduction was less marked by day 28, as blood antibody levels appeared to rebound. But when the researchers observed the mice lacking Tlr5 on the 85th day after vaccination, their antibodies seemed to have dipped again, suggesting that without this bacterial signaling, the effects of the flu vaccine wane more quickly.

The researchers saw similar results when they gave mice a polio vaccine, which, like the flu shot, uses an inactivated virus and doesn’t contain so-called adjuvants—additives that boost the body’s immune response. Pulendran and colleagues suggest that these weaker, adjuvant-lacking vaccines rely more heavily on bacterial signaling. (They didn’t see the same results with the live virus in the yellow fever vaccine, for example.)

No specific type of bacteria seemed more important than another in prompting the vaccine response. But further experiments showed a major role for macrophages—immune cells that display pieces of the virus to activate B cells and that can also recognize flagellin. Pulendran’s favored explanation is that flagellin manages to break through the lining of the intestines to circulate in the body and activate B cells and macrophages, amping up antibody production. But where and how the interaction happens “is a huge mystery,” he says. “We don’t have the full answer.”

However, what they do know presents some interesting possibilities for human vaccines. “I think the implications of the work are fairly broad,” says David Artis, an immunologist at Weill Cornell Medical College in New York City who was not involved in the study. “It tells us that the microbiome is an additional component [of the vaccine response] that we didn’t previously appreciate.” He notes that people in industrialized countries seem to get more protection from flu vaccines than do residents of developing countries—a phenomenon that could be partially explained by variations in their microbiomes, though genetics, diet, and previous infections probably also play a role.

He cautions that the group would need to expose the mice to flu after vaccination to confirm that bacterial signals influence the vaccine-induced resistance to the virus. But if it does, future vaccines could try to mimic the effect of bacteria to prompt a bigger immune response. Several groups are already exploring flagellin as a possible adjuvant, though Artis suspects it’s not the only important microbial protein in play.

The results also raise questions about the role of antibiotics in vaccine response, says Paul Thomas, an immunologist at St. Jude Children’s Research Hospital in Memphis, Tennessee. People who are taking antibiotics when they get vaccinated could see depressed antibody levels “for a long time after,” he says. He suggests a follow-up study to measure antibody levels in people who start antibiotic treatment before getting the flu vaccine. Pulendran says his group plans to do just that for their next experiment.

Anyone who has seen pictures or models of the human brain is aware that the outside layer, or cortex, of the brain is folded in an intricate pattern of “hills”, called gyri, and “valleys”, called sulci.

It turns out that the patterns of cortical folding are largely consistent across healthy humans, broadly speaking. However, disturbances in cortical folding patterns suggest deeper disturbances in brain structure and function.

A new study published in the current issue of Biological Psychiatry suggests that schizophrenia is associated with reductions in the complexity of the cortical folding pattern that may reflect deficits in the structural connections between brain regions.

“The cortical folding pattern itself may not be so important, but the disturbances in connections between brain regions implicated by the changes in cortical folding could provide critical clues to deficits in the integrity of brain circuits that contribute to symptoms and functional impairment in schizophrenia,” commented Dr. John Krystal, Editor of Biological Psychiatry.

The study, conducted by an international group of scientists, measured cortical folding using regional local gyrification index values in patients with psychotic disorders, their first-degree relatives, and healthy controls. The patient group included individuals with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder.

Local gyrification index is an advanced metric that quantifies cortical folding using a 3-dimensional approach.

Senior author Dr. Matcheri Keshavan, a Professor at Harvard Medical School, describes their results: “The main finding was that psychotic disorders are characterized by reduced folding of the cortex in key brain regions such as the cingulate cortex (a brain region involved in thinking and emotions). Reductions in cortical folding may reflect alterations in brain development early in life in these disorders. We also observed these alterations in first degree relatives at high risk for psychotic illnesses.”

With imaging data from 931 participants, this study is one of the largest of its kind and helps to resolve a diverse literature that has produced inconsistent findings, particular in studies of schizophrenia patients. With the consistency of this data in both the patient and relative groups, compared to the healthy group, this study suggests that hypogyria may mark familial risk for psychotic illnesses.

Thus, Keshavan added, “This study lays groundwork for further understanding of the causes of psychotic disorders.”

By Smitha MundasadHealth reporter, BBC News

In the largest study of its kind, scientists suggests this happens in one in every 19,000 operations.

They found episodes were more likely when women were given general anaesthesia for Caesarean sections or patients were given certain drugs.

Experts say though rare, much more needs to be done to prevent such cases.

‘Unable to move’

Led by the Royal College of Anaesthetists and Association of Anaesthetists of Great Britain and Ireland, researchers studied three million operations over a period of one year.

More than 300 people reported they had experienced some level of awareness during surgery – some recalled experiences from years ago.

Most episodes were short-lived and occurred before surgery started or after operations were completed. But some 41% of cases resulted in long-term psychological harm.

Patients described a variety of experiences – from panic and pain to choking – though not all episodes caused concern.

The most alarming were feelings of paralysis and being unable to communicate, the researchers say.

One patient, who wishes to remain anonymous, described her experiences of routine orthodontic surgery at the age of 12.

She said: “I could hear voices around me and I realised with horror that I had woken up in the middle of the operation but couldn’t move a muscle.

“While they fiddled, I frantically tried to decide whether I was about to die.”

‘Rare but concerning’

She told researchers that for 15 years after her operation she had had nightmares of monsters leaping out to paralyse her.

And it was only after she made the connection between this and her operation that the nightmares stopped.

Each person’s experience was analysed to identify factors that could make these situations more likely.

About 90% occurred when muscle-relaxant drugs – used to help paralyse muscles during surgery – were administered in combination with other drugs that normally dampen consciousness.

Researchers believe in some of these cases patients received an inappropriate balance of medication, leaving them paralysed but still aware.

And there were several reports of awareness from women who had Caesarean sections while under general anaesthesia.

Though this type of anaesthesia is most often used in emergency situations, researchers say women should be informed of the risks.

Drug errors

They calculate up to one in 670 people who have Caesarean sections with general anaesthesia could experience some levels of awareness.

But experts argue this is partly due to the balance needed when achieving unconsciousness for the woman while still keeping the baby awake.

Other common factors include lung and heart operations and surgery on patients who are obese.

And some 17 cases were due to drug errors.

Researchers are calling for a checklist to be used at the start of operations and a nationwide approach to managing patients who have these experiences.

Prof Tim Cook, at the Royal United Hospital in Bath, who led the research, said: “For the vast majority it should be reassuring that patients report awareness so infrequently.

“However for a small number of patients this can be a highly distressing experience.

“I hope this report will ensure anaesthetists pay even greater attention to preventing episodes of awareness.”