Childhood stress contributes to adult depression, study finds

Growing up in a stressful environment isn’t conducive to becoming a well-adjusted adult. Studies have shown that people who were constantly stressed out during childhood have an increased risk of being depressed.

How exactly are the two related? Stress at a young age permanently alters the expression of a key gene in the brain, resulting in a lifetime of elevated levels of a hormone that contributes to depression, according to a study published this week by the journal Nature Neuroscience.

To figure this out, a team of German researchers stressed out baby mice by separating them from their mothers for three hours a day during their first 10 days of life. Other mice were kept with their mothers continuously, to serve as controls.

All the animals got blood tests when they were six weeks, three months and one year old. The mice that had been removed from their mothers’ nests had higher levels of the stress-related hormone corticosterone circulating in their blood than their counterparts, the researchers found. When the animals were subjected to stressful situations, the traumatized mice also produced more corticosterone than the controls.

The researchers, from the Max Planck Institute of Psychiatry in Munich, found behavioral deficits in the stressed-out mice too. They were more likely to freeze up in forced swim tests, and had memory problems with certain tasks.

The researchers traced these problems to decreased methylation of a key section of the AVP gene, which prompted the mice to make too much of the hormone arginine vasopressin.

To confirm that arginine vasopressin was responsible for the stress, the researchers gave the mice a drug that blocked the hormone’s effects in the brain. When the drug was working, the stressed-out mice produced normal levels of corticosterone.

“Our results suggest that adverse events in early life can leave persistent epigenetic marks on specific genes that may prime susceptibility to neuroendocrine and behavioral dysfunction,” they concluded.

-- Karen Kaplan

Depressed pregnant women respond more strongly to flu viruses

Depressed pregnant women respond more strongly to the seasonal flu vaccine, producing higher levels of potentially damaging cytokines--a finding that could help explain why pregnant women have about six times the normal risk of hospitalization and complications from pandemic H1N1 influenza.  An immune overreaction to the virus is thought to be responsible for many of the complications of influenza.

Dr. Lisa Christian, a psychiatrist at Ohio State University, and her colleagues reported the finding today in the journal Brain, Behavior and Immunity. The results appear to emphasize the need for pregnant women to be immunized against swine flu. Typically, only about 12% to 13% of pregnant women are immunized against seasonal flu, and it is not clear that vaccination rates will be higher with swine flu, despite the clear risk of not doing so.

Pregnancy suppresses certain functions of the immune system to prevent rejection of the fetus and to protect the fetus from the inflammation that accompanies fevers and other illnesses. Christian and her colleagues had previously reported that depression in pregnant women and those subjected to other stressors can exacerbate the immune changes, leading to higher levels of various potentially damaging immune molecules in their blood stream.

In the new study, 22 pregnant women filled out a questionnaire about their depression symptoms and gave a blood sample before being immunized against seasonal flu. A second blood sample was obtained six to nine days later. The higher the women scored on the standardized test for depression symptoms, the higher the levels of immune molecules in their blood at the second assay. The elevations were mild, but the assumption is that levels would be much higher accompanying an actual flu infection. High levels of such inflammatory molecules have previously been linked to an increase in preterm births and in pre-eclampsia, which is characterized by high blood pressure and the potential death of the fetus and the mother.

Women who were unhappy about their pregnancies had significantly more symptoms of depression than those who were pleased. Women with less social support and more frequent hostile social interactions were also more likely to be depressed.

"Inflammatory responses to vaccination do no harm, are mild, and typically go away within a few days," Christian said. "But an extended inflammatory response to vaccination, such as the one seen in women with the most depressive symptoms, isn't expected, and it serves as a way to estimate how somebody might respond to an actual infection or illness." So get vaccinated.

-- Thomas H. Maugh II

Rodent of the Week: Light at night linked to depression

Lots of research suggests that our bodies are adapted to sleep during darkness and become active during daylight. Disruptions in circadian rhythms may increase the risk of metabolic diseases and some types of cancer. Now, a study in mice has found, being exposed to light at night for prolonged periods of time may contribute to depression.

Researchers at Ohio State University found that mice housed in a lighted room 24 hours a day exhibited more symptoms of depression than did mice that had a normal light-dark cycle. When mice that lived in constant light had the option to escape into an opaque tube, they showed fewer symptoms of depression than mice who did not have an escape from 24-hour light. The depression tests in mice involved things like measuring how much sugar water they drank.

One interesting twist in the study, however, revealed that mice housed in constant light seemed to have lower levels of anxiety; they had lower levels of corticosterone, a stress hormone linked to anxiety. But these mice may simply have adapted to the constant light, which resulted in fewer signs of anxiety, the researchers said.

The study contributes to the growing body of research that circadian rhythms are highly influential in health.

"The increasing rate of depressive disorders in humans corresponds with the increasing use of light at night in modern society," Randy Nelson, a co-author of the paper and professor of neuroscience, said in a news release. "Many people are now exposed to unnatural light cycles, and that may have real consequences for our health."

The study was presented this week at the annual meeting of the Society for Neuroscience in Chicago. It will be published in December in the journal Behavioural Brain Research.

-- Shari Roan

Photo: Advanced Cell Technology Inc.

Older antidepressant spurs more suicidal thinking in men than newer medication

The largest clinical trial to date comparing an older, tricyclic antidepressant with a newer antidepressant of the selective serotonin reuptake inhibitor (SSRI) class has found that the emergence of suicidal thinking was almost 10 times more common in men taking the older drug than in those taking the newer medication.

The study also found that for men and women taking either medication, suicidal thinking was spread over the first six weeks of treatment, but peaked at roughly the fifth week before declining significantly after week six. Taking place at academic medical institutions across Europe, the trial, called Genome-Based Therapeutic Drugs for Depression--or GENDEP--gauged the responses to antidepressants of 811 persons ranging from 18 to 72 with depression.

The results of the study, published in the British journal BMC Medicine, suggest that an older generation of antidepressant--still widely prescribed--is not without the risk of suicidal thoughts that is widely attributed to newer medications in the SSRI class. Indeed, for some populations, it may be far higher.

The study authors note that tricyclic antidepressants--in this case nortriptyline--can sometimes increase agitation and irritability--a feature of depression more commonly found in men in the first place. Exacerbating that agitation might make the tricyclic antidepressant nortriptyline a more powerful prompt to suicidal thoughts for some, they surmised.

The study also underscores an important lesson for patients starting on an antidepressant and the physicians who care for them: Earlier studies have suggested that suicidal thoughts were most frequent in the first couple of weeks of treatment or after a change in dose. But this European study suggests that suicidal thoughts continue--and indeed may escalate--into a patient's fifth or sixth week on a new antidepressant, before falling off. Patients and their families and physicians should continue to be watchful for changes in thoughts or behavior well into a new therapy.

-- Melissa Healy

Thursday is National Depression Screening Day

People who wish to be screened for depression can do so Thursday, Oct. 8, at one of 1,000 sites nationwide or by completing an online questionnaire. The annual screening day is sponsored by major mental health organizations, including the National Institute of Mental Health.

The screening is free and anonymous. Participants can also discuss the results of the screening with a mental health professional, receive information on depression and find out where they can receive additional help. The screening is not meant to diagnose depression but to steer people to qualified professionals who can provide a full assessment.

This year's event also includes specific information for college students and military personnel. Military installations will hold several events to provide screening and information on mental health issues of greatest concern to military personnel and their families, including post-traumatic stress disorder.

To locate a screening site or take the online screening, visit the National Mental Health Screening Day website.

-- Shari Roan

Photo credit: Kirk McCoy / Los Angeles Times

Mediterranean diet reduces depression, study suggests

Jetting to the sunny climes of the Mediterranean couldn't hurt if you feel a bout of depression settling in.

But a new study in the Archives of General Psychiatry finds that if your aim is to minimize your risk of depression in the first place, you might stay right where you are and make your plate look like it's been to the Mediterranean. You should scale back on the meats and dairy fats, eat some nuts, and increase your consumption of fish, vegetables and legumes doused in olive oil.

Oh, and pour yourself a glass of wine. Not half a bottle; one glass, maybe two.

The Mediterranean diet has been linked to reduced risk of heart disease, stroke, Type 2 diabetes and cancer. it was only a matter of time before researchers would begin to wonder whether a Mediterranean diet could also reduce the risk of depression -- which, like all of the above diseases, is linked to higher levels of inflammation throughout the body. They found tantalizing suggestions of such a link: Compared with Northern Europe, the countries surrounded by the Mediterranean report lower rates of mental illness and suicide. 

The study linking adherence to a traditional Mediterranean diet with reduced depression risk is the first to test that link prospectively. It followed a group of subjects over several years, tracked their eating patterns and recorded how many reported several symptoms or a diagnosis of depression. This one tracked 10,094 graduates of the University of Navarra in Spain for roughly 4 1/2 years and found that the more closely subjects stuck to the principal elements of a Mediterranean diet, the lower their likelihood of developing depression.

So what is it -- the sunshine, the hillside towns that keep even octogenarians walking daily on errands? The tradition of far niente? The wine, the fish, the nuts, the legumes, the olive oil? While acknowledging that lifestyle factors or genetics may contribute to the lowered risk of depression, the researchers focused largely on the dietary components, and sought to single out one or two more powerful than the others in warding off depression.

In the end, they noted, "the role of the overall dietary pattern may be more important than the effect of single components." They even suggested that depression may yield in the face of a "synergistic combination" of polyunsaturated fats from olive oil and nuts, antioxidants from fruits and flavenoids, B vitamins and natural folates from vegetables and wine.

-- Melissa Healy

First, scan the brain; second, assess the antidepressant

As the L.A. Times reported recently in its special Health issue on depression: "A good way to speed up the process of finding an effective antidepressant would be to learn sooner whether a particular drug was going to work."

That story, "Brain tests could predict antidepressant efficiency," noted that researchers were experimenting with noninvasive ways -- such as imaging tests and electrophysiologic studies -- to assess how the brain responds to the medications. 

The results from one such study have now been reported in the September issue of the journal Psychiatry Research. And the authors, from UCLA, say they suggest an ability to assess within a week whether a particular drug might work. In depression, a week is a long time.
 
The study, conducted at nine sites around the country and involving 375 depressed people, measured brain wave patterns before -- and after -- a week of Lexapro use. The researchers were looking for changes in brain activity that come well before a depressed person's mood actually improves.

The researchers ultimately were able to predict medication effectiveness with 74% accuracy, they said.

Here's the full story from UCLA, in which lead author Dr. Andrew Leuchter calls the results "a milestone in our efforts to develop clinically useful biomarkers for predicting treatment response in MDD." (That would be "major depressive disorder.")

As a related story in Health's depression issue noted: "Treating depression can be hit or miss. Doctors have more than 20 medications to choose from. But finding the right one is a process of trial and error."

Such results may lead to less error.

Researchers reported in the August issue of Archives of General Psychiatry that antidepressants are the most commonly prescribed class of drugs in the country. In 1996, 5.84% of people age 6 and older were taking the drugs. In 2005, 10.15% were.  

-- Tami Dennis

Credit: Photo illustration by Kirk McKoy / Los Angeles Times

Crabby kids = depressed adults?

Irritability in childhood has long been suspected of being a potential symptom of depression. A new study confirms this link.

Researchers at the National Institute of Mental Health questioned the parents of 631 teen-agers, whose average age was 13.8, about irritability in their children. Twenty years later, the same children, now adults, were assessed for mood and anxiety disorders. The people who were irritable kids were more likely to be adults with depression or anxiety. However, irritability in adolescence did not predict later development of bipolar disorder or other serious mental health disorders.

The study found that irritability and arguing with parents and teachers were strongly linked in adolescence. Anger or tantrums in reaction to parents' requests were strong predictors of major depression or anxiety disorders in adulthood as was arguing with teachers. Irritable youths were more likely to have a lower income and educational attainment as adults.

Irritability is the tendency to react with anger, grouchiness or tantrums that are disproportionate to the situation. Some studies estimate that about 5% of youths, ages 8 to 19, are irritable while in adults the prevalence is thought to be slightly less. The researchers note that studies on irritability are scarce. But  they wrote: "These data suggest that irritability occupies a position at the interface between emotional and disruptive behavior problems."

The study is published in the September issue of the American Journal of Psychiatry.

-- Shari Roan

Photo credit: Brian Vander Brug  /  Los Angeles Times

College students pack a heavy bag of mental illness

Loading up the car for college? The American Psychiatric Assn. reminds us that while college can be a time of great hope and exuberance, that's not always the case: Its 2008 American College Health Assn. Survey found that 30% of college students reported that at some point in the last 12 months, they had felt so depressed it was hard to function. And 49% reported that in the same period, they had experienced overwhelming anxiety.

Ten percent of those surveyed said they had been diagnosed or treated for depression, and 6% reported they had seriously considered suicide. And a study published December 2008 in the Archives of General Psychiatry found that alcohol disorders affected roughly one in five college students. The next-most-common class of disorders were personality disorders, affecting about 17.7% of college students.

We know from the website Active Minds, devoted to "changing the conversation about mental health on college campuses" and to providing mental-health resources to college students, that an average of 1,100 college students die by suicide each year. Sure, there's beer-pong and all-night partying. But there's crushing pressure as well, and it can take a toll on students' mental health. (To find a chapter, or start one on your campus, look here.)

The Los Angeles Times' Shari Roan wrote back in September 2007 about the growing demands on college mental health services, and some of the dilemmas they face in serving troubled students on the cusp of adulthood. Now would be a good time for parents and students alike to revisit that article. 

-- Melissa Healy

Pregnant, depressed and confused? New guidelines clarify antidepressant risks, benefits

Depression hits women in the childbearing years more than any other demographic, but how to deal with this most common of mental afflictions poses a conundrum: antidepressant medications have become the first line of defense against depression; but there's growing research evidence that they pose risks to a developing fetus.

It's a tightrope that obstetricians on the front lines of patient care have walked for years without guidance from their own leaders or the profession of psychiatry. Busy, concerned but operating in unfamiliar terrain, many obstetricians have pulled out their pads, written a prescription for an antidepressant, and hoped for the best. No surprise, then, that by 2003, 13% of pregnant women had taken an antidepressant at some point in their pregnancy -- twice the rate that was seen in 1999.

But on Friday, the American Psychiatric Assn. and the American College of Obstetricians and Gynecologists put a safety net under obstetricians and the pregnant women they treat. In a first-ever set of guidelines, the two physician groups offered obstetricians and their patients a set of clear road maps for treating depression in pregnancy.

The guidelines were published simultaneously in the ACOG journal Obstetrics and Gynecology and in the APA's journal, General Hospital Psychiatry.

The upshot: For many pregnant women showing signs of depression, talk therapy can help manage symptoms with no risk to a developing fetus and good prospects of success. But for some, including those who are suicidal, have a personal history of disabling depression, or also suffer from more serious mental illness such as bipolar disorder or psychosis, the benefits of antidepressants are likely to outweigh the drugs' risks to a developing fetus.

The guidelines provide a comprehensive review and assessment of the research findings that exist on the risks that antidepressant medications pose for babies before and after birth. But they also take account of another, less conclusive body of research findings: those that suggest that having a severely depressed mother can be bad indeed for a baby before and after birth and well into his or her childhood.

Dr. Charles Lockwood, a professor of obstetrics at Yale University and one of the guidelines' nine authors, hailed the joint venture as a call to obstetricians to look routinely for signs of depression in their patients of childbearing age and for psychiatrists to step up to their role in the care of such women. Noting that roughly four of five women of childbearing age consider their ob/gyn a primary care physician,  Lockwood said obstetricians are "uniquely positioned" to intervene early in depression. That will improve the physical and mental well-being not only of women over their lifespans, but their children's as well, he said.

Dr. Sudeepta Varma, a psychiatrist at New York University's Langone Center, said her profession has too long left obstetricians on their own to care for depressed patients -- a lack of involvement she believes will change with the issuance of the new guidelines.

"I think psychiatrists have been reluctant to take on the care of pregnant patients," said Varma. The new guidelines should make psychiatrists and mental health professionals "more comfortable" in doing so. She added that they should prompt a greater interest on the part of obstetricians, as well, to develop professional relationships with psychiatrists and psychotherapists, and to seek their help more routinely in sorting through a depressed patient's options. 

"We should have more communication with each other," she said.

-- Melissa Healy