Arizona Family Resource Counseling Center

Maintenance Treatment Crucial for Teens’ Recovery from Depression

Long-term maintenance treatment is likely to sustain improvement and prevent recurrence among adolescents with major depression, according to an NIMH-funded study published in the April 2008 issue of the Archives of General Psychiatry.

The study, led by Paul Rohde, Ph.D., of Oregon Research Institute, analyzed data from the Treatment of Adolescents with Depression Study (TADS), a large, NIMH-funded trial in which depressed teens were randomized to one of three treatments for 36 weeks—fluoxetine (Prozac), cognitive behavior therapy (CBT) or a combination of both.

Teens with depression, even if they show a good initial response to treatment, are at high risk for relapse and recurrence. However, guidelines for depression maintenance treatment are based on adult needs. Rohde and colleagues aimed to identify whether the available guidelines are appropriate for depressed adolescents.

Among the 242 TADS participants analyzed for this study, 61 percent significantly improved by week 12. The combination group achieved the highest rate of sustained response (71 percent) compared to the fluoxetine-only group (68 percent) and CBT-only group (42 percent).

The majority (82 percent) of teens who reached a sustained positive response by week 12 maintained this level of recovery through week 36. Among those in combination treatment, about 89 percent maintained improvement for the full 36 weeks. Among those in the fluoxetine-only group, 74 percent maintained improvement, but among those in CBT-only treatment, 97 percent maintained their improvement.

The high long-term success rate of CBT suggests that for teens who initially respond to it, CBT may have a preventive effect that helps to sustain positive improvement and potentially avoid relapse or recurrence, even if treatment visits become infrequent, as was the case after the first 12 weeks in the TADS study. Additionally, the relatively lower sustained success rate for fluoxetine suggests that the effectiveness of fluoxetine therapy may plateau at a certain point for some responders, triggering a need for the addition of psychosocial treatment.

“For those teens who respond to fluoxetine only, adding CBT to their treatment regimen early on would likely increase their chances for continued improvement,” suggested Rohde.

The findings help guide clinicians in deciding on the best maintenance course after a teen responds to an initial treatment. They also emphasize the value of ongoing, long-term treatment, even if treatment visits are infrequent, Rohde and colleagues concluded.

Reference

Rohde P, Silva SG, Tonev ST, Kennard BD, Vitiello B, Kratochvil CJ, Reinecke MA, Curry JF, Simons AD, March JS. Achievement and maintenance of sustained improvement during TADS continuation and maintenance therapy. Archives of General Psychiatry. 2008 Apr; 65(4): 447-455.

Anxious Youth Have Disturbed Brain Responses When Looking at Angry Faces

When looking at angry faces so quickly that they are hardly aware of seeing them, youth with generalized anxiety disorder (GAD) have unchecked activity in the brain’s fear center, say NIMH researchers. This disturbance is greater in those who are more severely anxious.

These findings were reported in an article in the May 2008 issue of the Archives of General Psychiatry by NIMH-funded investigator Christopher S. Monk, Ph.D, of the University of Michigan, and colleagues at the University of California, Los Angeles; University of Southampton, Southampton, UK; Georgia State University, Atlanta; and NIMH in Bethesda, Md.

The investigators used functional magnetic resonance imaging, a brain-scanning technique that shows increases in blood flow when regions of the brain become active, to study changes in the regions of the brain after the participants saw pictures of angry faces. These pictures were shown so quickly—only 17 thousandths of a second—that the participants hardly saw them. The participants included 17 children and adolescents with GAD and 12 who were healthy.

The scans showed that increased anxiety is associated with increased activation of the brain’s fear center, the amygdala. This almond-shaped structure, deep in the brain, triggers a fear or anxiety response, and alerts the rest of the brain that a threat is present.

Scientists believe that the amygdala is normally kept in check by the brain’s executive hub, the prefrontal cortex, which is located behind the eyes and the forehead. The scans showed that the executive hub’s control over the fear center is weakened in the anxious participants. The scans also showed that the executive hub has the least control in the most anxious participants.

The researchers concluded that in youth with GAD, the fear center overreacts because the executive hub fails to control it.

This study is believed to be the first report of brain responses in anxious youth looking at angry faces so quickly that they are hardly aware of seeing them. Other investigators found increased activation of the amygdala when adults with post-traumatic stress disorderare quickly exposed to fearful faces.

Reference

Monk CS, Telzer EH, Mogg K, Bradley BP, Mai X, Louro HM, Chen G, McClure-Tone EB, Ernst M, Pine DS. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Archives of General Psychiatry. 2008 May;65(5):568-576.

Depression Linked to Bone-Thinning in Premenopausal Women

Should Be Considered Risk Factor for Osteoporosis; Immune System Involved

Premenopausal women with even mild depression have less bone mass than do their nondepressed peers, a study funded in part by the National Institute of Mental Health (NIMH), part of the National Institutes of Health (NIH), shows. The level of bone loss is at least as high as that associated with recognized risk factors for osteoporosis, including smoking, low calcium intake, and lack of physical activity.

Hip bones, the site of frequent fractures among older people, were among those showing the most thinning in depressed premenopausal women. The reduced bone mass puts them at higher risk of these costly, sometimes fatal fractures and others as they age, the researchers note in the November 26 issue of the Archives of Internal Medicine. The report was submitted by Giovanni Cizza, MD, PhD, MHSc, of NIMH and the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Farideh Eskandari, MD, MHSc, of NIMH; and colleagues.

“Osteoporosis is a silent disease. Too often, the first symptom a clinician sees is when a patient shows up with a broken bone. Now we know that depression can serve as a red flag – that depressed women are more likely than other women to approach menopause already at higher risk of fractures,” said NIMH Deputy Director Richard Nakamura, PhD.

After bone mass reaches its peak in youth, bone-thinning continues throughout life, accelerating after menopause. Preliminary studies had suggested that depression may be a risk factor for lower-than-average bone mass even in young, premenopausal women. Results of the current study lend considerable weight to those earlier findings. The study’s design reduced the possibility that the lower bone mass was linked to factors other than depression.

Study participants included 89 depressed women and 44 nondepressed women, for comparison. All were between 21 and 45 years old and were premenopausal. Except for depression, the two groups were similar in risk factors, including calcium, caffeine, and alcohol intake; smoking; level of physical fitness; use of oral contraceptives; and age of first menstrual period. Both groups were of relatively high socioeconomic status and were well nourished.

One difference was that the depressed women were taking antidepressant medications. A previous study suggested that older adults taking antidepressants called selective serotonin reuptake inhibitors had more bone fractures than others. However, the current study showed that these medications were not linked to low bone mass in premenopausal women.

The researchers found that 17 percent of the depressed women had thinner bone in a vulnerable part of the hip called the femoral neck, compared with 2 percent of those who were not depressed. Low bone mass in the lumbar spine, in the lower back, was found in 20 percent of depressed women, but in only 9 percent of nondepressed women. Bone mass was measured via an X-ray technique called DXA scanning.

There was no significant link between the degree of bone loss and the severity of depression or the cumulative number of depressive episodes, the researchers found. The depressed women had been diagnosed with mild depression and were having, or had recently had, a depressive episode.

“Depression generally isn’t on clinicians’ radar screens as a major risk factor for osteoporosis, particularly for premenopausal women. It should be,” said Cizza.

Blood and urine samples also showed that depressed women have imbalances in immune-system substances, including those that produce inflammation, compared to their healthy peers. This additional finding strengthens the case for a suspected link between depression-induced imbalances in the immune system and accelerated bone loss. The blood and urine samples were taken every hour for a full day, providing a truer picture than does less frequent testing, as had been done in previous studies.

The immune-system imbalances may be tied to excess adrenalin, since the part of the nervous system that produces adrenalin is over-active in depressed people. Increased adrenalin can over-stimulate the immune system. Compared to the others, the depressed women in this study had higher levels of immune-system proteins that promote inflammation, and lower levels of those that prevent it.

One of these inflammation-promoting proteins, IL-6, is known to promote bone loss. At the molecular level, bones routinely break down, and their minerals, notably calcium, are reabsorbed into the blood, where they travel throughout the body to perform crucial functions in cells. At the same time, the body builds the bone back up. Imbalances in this normal loop of bone re-absorption and build-up, such as high levels of IL-6, could promote bone loss, the researchers suggest.

Symptoms Persist as Bipolar Children Grow Up

Follow-up Study Confirms Continuity of Child and Adult Forms

Bipolar disorder (BD) identified in childhood often persisted into adulthood in the first large follow-up study of its kind. Forty-four percent of children diagnosed with BD continued to have manic episodes as adults, in the study by NIMH grantee Barbara Geller, M.D., and colleagues at Washington University in St. Louis. They report on their findings in the October issue of the Archives of General Psychiatry.

“Serious mental illnesses do not emerge de novo (anew) when individuals reach adulthood, but rather reflect early developmental processes,” explained NIMH’s Ellen Leibenluft, M.D., in an accompanying editorial entitled “Pediatric Bipolar Disorder Comes of Age.”

Background

The rates of youth diagnosed with BD have soared over the past decade, amid debate over whether the diagnosis is used excessively. To learn more about the course of the disorder and what affects it, Geller and colleagues separately interviewed 108 children diagnosed with BD at about age 11 and their parents, periodically over eight years, by which time half of the patients had become adults.

Results of This Study

Among these 54 young adult patients, 44 percent had at least one manic episode after age 18. This was 13 to 44 times the population average. Thirty-five percent had substance use disorders. These rates are comparable to those seen in studies of adults with the disorder, according to the researchers. During the eight years, 88 percent of all patients experienced periods of recovery from mania, but 73 percent of these relapsed. Children with BD were ill with mania or depression about 60 percent of the time.

Significance

The study adds to mounting evidence for the legitimacy of the diagnosis of BD in children, and reflects the “field’s continuing efforts to nurture developmental conceptualizations of psychiatric illnesses,” notes Leibenluft. The results are consistent with a 2006 study by Geller and colleagues, which found that child and adult forms of BD occurred within the same families. In taking stock of what has been learned about pediatric BP over the past couple of decades, Leibenluft points to a growing consensus that “unequivocal,” classic BD occurs in youth – albeit with continuing debate about whether children with persistent, severe irritability, but without distinct episodes of mania, should be assigned the BD diagnosis. There is also consensus that children with BD are severely impaired, with frequent relapses and other apparent psychopathology.

What’s Next?

Neuroimaging and genetics studies hold hope for development of biomarkers that will refine diagnosis, speed development of more specific treatments – and someday even “prevent the onset of BD in youth at risk,” says Leibenluft.

References:

Geller B, Tillman R, Bolhofner K, Zimerman B. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome. Arch Gen Psychiatry. 2008 Oct;65(10):1125-33.

PMID: 18838629

Leibenluft E. Pediatric bipolar disorder comes of age.

Arch Gen Psychiatry. 2008 Oct;65(10):1122-4. No abstract available. PMID: 18838628

Geller B, Tillman R, Bolhofner K, Zimerman B, Strauss NA, Kaufmann P. Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity.

Arch Gen Psychiatry. 2006 Oct;63(10):1130-8. PMID: 17015815

Premature Birth Risk Higher for Pregnant Women Taking SSRIs or Suffering from Untreated Depression

Untreated major depression, as well as the use of antidepressant medications, may increase the risk for premature (preterm) birth, but the risk of other problems in fetuses such as breathing, gastrointestinal, or motor problems, may not be increased, according to a study of pregnant women published online ahead of print March 15, 2009, in the American Journal of Psychiatry.

Background

Use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), is common among women of childbearing age. Although there is some concern regarding the use of SSRIs during pregnancy and their effects on the growing fetus, research results have been mixed. Overall, it appears the risk for major birth defects is very low, but the risk for other complications, such as minor physical anomalies—a specific type of birth defect—or preterm birth (before 37 weeks gestation), has not been consistently established.

Katherine L. Wisner, M.D., of the University of Pittsburgh, and colleagues aimed to determine whether the use of SSRIs or the existence of major depression during pregnancy was associated with minor physical anomalies in the baby, low infant birth weight, preterm birth or other issues. In this observational study, the researchers categorized 238 pregnant women in Cleveland, Ohio, and Pittsburgh, Pa., into one of three groups:

no use of SSRIs and no major depression during pregnancy (131 women);

use of SSRIs either at some point (23 women) or throughout the pregnancy (48 women);

those who had major depression—either at some point (22 women) or throughout the pregnancy (14 women)—but who remained unmedicated.

The researchers gave general advice to the women about managing major depression and use of SSRIs, but they did not interfere in treatment decisions made by the women and their doctors. Wisner and colleagues examined various outcomes, such as maternal weight gain, pregnancy duration, minor physical anomalies in the infant, infant birth weight, and other infant characteristics.

Results of the Study

Wisner and colleagues found that for both pregnant women with untreated major depression and for those who were taking SSRIs throughout their pregnancy, more than 20 percent of infants were delivered preterm. In comparison, only 4 percent of infants partially exposed to SSRIs during gestation and 6 percent not exposed at all to SSRIs or depression during gestation were delivered pre-term.

Neither the use of SSRIs nor major depression was associated with an increase in minor physical anomalies; short-term medication-associated issues like breathing, gastrointestinal or motor problems; or reduced weight gain among the women during pregnancy. Birth weight of infants also did not differ across groups.

Significance

The results support other studies that have found a link between continuous SSRI treatment and an increase in risk of preterm birth, but they are not consistent with studies that have found an increased risk of drug-associated issues in infants exposed to SSRIs while in the womb. However, the researchers note that untreated depression among pregnant women may present the same risk to infants as SSRI use, reiterating the need for doctors to work with individual patients to balance the risks and benefits of SSRI use and the treatment of major depression during pregnancy.

What's Next?

More research is needed to better determine whether women with major depression who are treated with SSRIs and experience remission during pregnancy have more favorable outcomes compared to unmedicated depressed women. In addition, larger studies may be able to determine differences in outcomes among SSRIs. Finally, more research into non-medication interventions for treating depression during pregnancy, including psychotherapy and other approaches, is also needed.

Reference

Wisner KL, Sit DKY, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. American Journal of Psychiatry. Online ahead of print March 15, 2009.

National Survey Confirms that Youth are Disproportionately Affected by Mental Disorders

About 20 percent of U.S. youth during their lifetime are affected by some type of mental disorder to an extent that they have difficulty functioning, according to a new NIMH survey published in the October 2010 issue of the Journal of the American Academy of Child and Adolescent Psychiatry. The data support the observation from surveys of adults that mental disorders most commonly start in early life.

Background

Many regional surveys conducted in the United States have indicated that about one in four to five children experience a mental disorder sometime in their life. But until now, no nationally representative surveys had been conducted to determine if these prevalence rates of a wide range of mental health problems hold true across the nation.

Kathleen Merikangas, Ph.D., of NIMH and colleagues analyzed data from the National Comorbidity Study-Adolescent Supplement (NCS-A), a nationally representative, face-to-face survey of more than 10,000 teens ages 13 to 18. They used standard diagnostic criteria set by the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-IV) to determine lifetime prevalence of mental disorders among the teens. To follow up on the teens' responses, they also collected data via mailed questionnaires completed by one parent or guardian of each teen surveyed.

Results of the Study

Overall, nearly half of the sample reported having met diagnostic criteria for at least one disorder over a lifetime, and about 20 percent reported that they suffered from a mental disorder with symptoms severe enough to impair their daily lives. In addition,

11 percent reported being severely impaired by a mood disorder (e.g., depression or bipolar disorder),

10 percent reported being severely impaired by a behavior disorder such as attention deficit hyperactivity disorder or conduct disorder,

8 percent reported being severely impaired by at least one type of anxiety disorder.

In addition, about 40 percent of those who reported having a disorder also met criteria for having at least one additional disorder. Those with a mood disorder were more likely than others to report having a coexisting disorder. Underscoring the notion that mental disorders manifest early in life, the researchers also found that symptoms of anxiety disorders tended to emerge by age 6, behavior disorders by age 11, mood disorders by age 13, and substance use disorders by age 15.

The researchers also noted strong links between parental characteristics and their teen's disorders. For example, children of parents with less education (e.g., no college degree) were at an increased risk for having any kind of mental disorder. And compared to teens with married or cohabiting parents, those with divorced parents also were at higher risk for a disorder, especially anxiety, behavior and substance use disorders.

Significance

The NSC-A results provide a broader and longer-term outlook compared with last year's National Health and Nutrition Examination Survey (NHANES), which asked respondents about diagnosed disorders and service use within a 12-month window only, and was limited to six disorders.

According to the NCS-A researchers, the percentage of youth suffering from mental disorders is even higher than the most frequent major physical conditions in adolescence, including asthma or diabetes. The results reiterate the importance of developing prevention strategies and promoting early intervention for at-risk children and adolescents.

What's Next

More research is needed to better understand the risk factors for developing a mental disorder in youth, as well as how to predict which disorders may continue into adulthood. In addition, the researchers acknowledge the need for more prospective research to tease apart the complex interplay among socioeconomic, biological and genetic factors that may contribute to the development of mental disorders in youth.

Reference

Merikangas KR, He J, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J. Lifetime prevalence of mental disorders in U.S. adolescents: Results from the National Comorbidity Study-Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry. 2010 Oct. 49(10):980-989.