The Mental Health Social Worker

ScienceDaily (Feb. 20, 2010) — More than half of low-income urban mothers met the criteria for a diagnosis of depression at some point between two weeks and 14 months after giving birth, according to a study led by University of Rochester Medical Center researchers and published online by the journal Pediatrics.

This is the first study to describe the prevalence of depression among low-income urban mothers, who were attending well-child care visits, through the use of a diagnostic interview. It also is the first study of this population group to test the accuracy of three depression screening tools routinely used by physicians.

The screening tools have high accuracy in identifying depression, the researchers concluded, but cutoff scores may need to be altered to identify depression more accurately among low-income urban mothers.

The study involved 198 mothers who were 18 years of age or older and whose children were no older than 14 months. The mothers attended well-child visits at the outpatient pediatric clinic at Golisano Children’s Hospital at the Medical Center.

The researchers found that 56 percent of the mothers, after a diagnostic interview, met the criteria for a diagnosis of a major or minor depressive disorder.

“This is an unexpected, very high proportion to meet diagnostic criteria for depression,” said Linda H. Chaudron, M.D., associate professor of Psychology, Pediatrics and of Obstetrics and Gynecology. “This may be a group at high risk for depression. The message of this study is that pediatricians and other clinicians who work with low-income urban mothers have multiple screening tools that are easy to use and accurate. These tools can help clinicians identify mothers with depression so they can be referred for help.”

Many women experience the so-called “baby blues.” When the feelings persist or worsen it may be clinical depression. The symptoms include insomnia, persistent sadness, lack of interest in nearly all activity, anxiety, change in appetite, persistent feelings of guilt, and thoughts of harming oneself or the baby. Postpartum depression affects up to 14 percent of new mothers in the United States, with higher rates among poor and minority women.

The researchers evaluated three screening tools, the Edinburgh Postnatal Depression Scale, the Beck Depression Inventory II and the Postpartum Depression Screening Scale, using the diagnostic interviews for validation.

The three screening tools have been evaluated in many populations, but one of the reasons the study was done was to test the tools with a group for whom there is not much data — low-income women, especially African-American women, Chaudron said. The researchers also evaluated the validity of the screening tools at various times during the postpartum year.

“The screening tools are valid when used anytime during the postpartum year,” Chaudron said.

Use of traditional cutoff scores may not be as accurate as previously thought. Clinicians should be aware that scores two or three points below traditional cutoff scores may indicate a need for further evaluation, the researchers concluded.

The study was funded by a grant from the National Institute of Mental Health.

Having a parent with HIV/AIDS or losing one or both parents to the illness leads to poorer mental health among children in China, according to a recent study funded in part by NIMH. Published in the November-December 2009 issue of the Journal of Pediatric Psychology, the study also emphasizes the need to develop culturally and developmentally appropriate measures and interventions for diverse populations.

Background

Most studies on HIV/AIDS have focused on conditions in U.S. inner cities and sub-Saharan Africa. Despite this lack of research attention, the AIDS epidemic in China and other Asian countries is rapidly growing.

Led by Xiaoming Li, Ph.D., of Wayne State University, researchers in China and the United States collaborated on a study to better understand the impact of parental HIV/AIDS on the emotional well-being of children. The researchers assessed 1,625 children, ages 6-18, living in two rural counties in central China, where many residents had been infected with HIV through unsafe blood collection practices.

Among the participants, 755 children had lost one or both parents to AIDS and 466 “vulnerable” children lived with HIV-infected parents. A comparison group of 404 children from the same community who did not have a HIV/AIDS-related illness or death in their immediate families were also included.

Results of the Study

As a group, children orphaned or made vulnerable by parental HIV/AIDS scored significantly higher on measures of depression and loneliness, and significantly lower on self-esteem, positive future expectations, hopefulness about the future, and perceived control over the future, than children in the comparison group. HIV/AIDS orphans were more likely to be depressed than vulnerable children, but the latter reported greater loneliness and lower self-esteem.

Children who lost one parent to HIV/AIDS showed similar rates of mental health problems as those who lost both parents, suggesting that having a surviving parent may not provide a significant protective effect on the emotional costs of losing a parent to HIV/AIDS.

Among HIV/AIDS orphans, the type of care setting—living in an orphanage, group home, or with kin—also affected their psychosocial adjustment. Group homes in China are managed by local adults serving the role of house parents for four to six orphans who refer to each other as siblings and the house parents as mother and father. HIV/AIDS orphans living in small group homes reported less depression and higher perceived control over their futures, but greater loneliness and lower self-esteem than those living in orphanages or with kin. Those living in orphanages showed greater hopefulness and expectations for the future compared with children in kinship care.

Significance

In one of the first efforts to assess the psychological well-being of Chinese children orphaned or made vulnerable by parental HIV/AIDS, the study shows that parental illness or death due to HIV/AIDS causes considerable psychosocial stress. Having a surviving parent does not appear to reduce this stress, but a child’s care setting may help moderate it.

The findings also suggest a range of factors that may affect the emotional well-being of Chinese children orphaned by HIV/AIDS. For example, unlike orphanages or kinship care, group homes seem to provide a more family-like atmosphere in the children’s own community, which may be more supportive of their mental health needs. Also, children in kinship care may have faced greater hardships than they’d previously experienced, due to increased financial strain on kinship households. These distinctions likely vary by culture—for example, HIV/AIDS orphans in African countries are predominantly cared for by kin or in community-based orphan care.

Though parental death is clearly a risk factor for emotional adjustment issues, some orphans in this study did not show higher levels of mental health problems compared with children living with an HIV-infected parent or those with no HIV/AIDS-related illness in their families. According to the researchers, this finding may demonstrate children’s natural resilience to highly stressful situations, as suggested by many past studies.

The researchers also caution that their findings may not apply to different populations within China or elsewhere. Factors such as cultural, ethnic, or socioeconomic background, or more common modes of HIV infection, such as unsafe sex or intravenous drug use, may affect a child’s psychosocial adjustment to parental death.

What’s Next

Further studies can help identify protective factors that promote better psychosocial adjustment in the face of living with or losing a parent to HIV/AIDS. Additional studies in this field may also improve scientists’ understanding of factors that influence the experience of bereavement and grief among children in China and other Asian countries. The researchers also emphasized the need to develop culturally appropriate measures and interventions for this diverse population.

Reference

Fang X, Li X, Stanton B, Hong Y, Zhang L, Zhao G, Zhao J, Lin X, Lin D. Parental HIV/AIDS and psychosocial adjustment among rural Chinese children. J Pediatr Psychol. 2009 Nov-Dec;34(10):1053-62. Epub 2009 Feb 10. PubMed PMID: 19208701; PubMed Central PMCID: PMC2782251.

An HIV-prevention program targeted at women receiving prenatal care may effectively reduce risks for HIV, sexually transmitted infections (STIs), and unplanned future pregnancies, according to NIMH-funded researchers. Bundling such interventions into existing health care models, like prenatal care, also may be more accessible to those who may not have the time, interest, or resources to attend a stand-alone HIV prevention program. Changing the way prenatal care is provided also may create sustainable advantages in reproductive health for all at-risk women. The study was published in the November 2009 issue of the American Journal of Public Health.

Background

The very behaviors that put young women at risk for pregnancy also put them at risk for STIs. Since they are no longer trying to prevent pregnancy, young, pregnant women are less likely to use condoms than their non-pregnant peers. This, in turn, puts them at high risk for contracting HIV and other STIs during and shortly after pregnancy. However, few HIV interventions have been developed to address the specific needs of young, pregnant women.

For their study, Jeanette Ickovics, Ph.D., of Yale University, and colleagues recruited 1,047 teens and young women (ages 14-25). All participants were in their second trimester of pregnancy and receiving prenatal care at one of two clinical sites during 2001-2004. The researchers randomly assigned the study participants to one of three care groups:

• Standard CenteringPregnancy group prenatal care
• CenteringPregnancy group prenatal care + HIV prevention components
• Standard individual prenatal care

CenteringPregnancy consisted of 10 two-hour sessions led by a midwife or obstetrician. During the sessions, women receive their prenatal care, engage in self-care activities (such as documenting their own weight and blood pressure), and attend a group discussion of important issues related to prenatal care, childbirth preparation, and postpartum care.

“CenteringPregnancy Plus” offered the same general content and structure of CenteringPregnancy, but three of the 10 sessions included 40 minutes of content related to preventing HIV. The HIV prevention components addressed the participants’ perception of HIV risk, personal goals for safer sex behaviors during and after pregnancy, and skills for communicating about safer sex behaviors with sexual partners.

Study participants receiving standard individual prenatal care met with their health care providers on the same schedule and the same number of times as women in the other two care groups, but they only spent about 10-15 minutes with their prenatal care provider per appointment, as is considered standard.

After the initial assessment, the researchers conducted follow-up interviews for all participants during the third trimester, and at six and 12 months after postpartum.

Results of the Study

Participants who received CenteringPregnancy Plus were 51 percent less likely to become pregnant again within six months of giving birth, compared with women in the two other care groups. The CenteringPregnancy Plus program also increased condom use and safe sex communication between partners, and reduced incidences of unprotected sex, compared with the other study treatments.

Teens (ages 14-19) who received CenteringPregnancy Plus had significantly fewer new STIs than teens in the other study conditions (9 percent vs. 12.5 percent of teens in the CenteringPregnancy group and 20 percent in the standard care group). There were no differences in infection rates among young adults (ages 20-25) in the study.

Significance

According to the researchers, CenteringPregnancy Plus differs from other HIV interventions by integrating sexual risk prevention into the existing structure of prenatal care, drawing on women’s motivations for a healthy pregnancy and their frequent contact with care providers.

Offering an HIV prevention program within the context of prenatal care may help to reduce the spread of HIV and other sexually transmitted infections by reaching an at-risk population that may not otherwise have had access to such programs. The researchers noted that the added time needed to deliver the HIV prevention did not come at the expense of prenatal care. However, they further cautioned that while the program was effective, the differences between groups were modest.

Past research has shown that among teenagers, repeat pregnancy shortly after giving birth increases parenting-related stress and negative parenting behaviors. Thus, by reducing or preventing repeat pregnancies, CenteringPregnancy Plus may help to improve the quality of life of young mothers and their children. The researchers suggest booster sessions of the program may prolong this effect beyond six months postpartum.

What’s Next

The researchers note that pregnancy may be an important window of opportunity to promote changes in behavior and improve the health of women. This study demonstrates the possibility of creating integrated programs that positively influence a wide range of health problems, rather than dealing with each problem separately. Such research may impact the design and delivery of future prenatal care services.

Dr. Ickovics and co-author Trace Kershaw, Ph.D., are conducting a follow-up study, also funded by NIMH, to test the “real-world” effectiveness of CenteringPregnancy Plus when provided through 14 New York City community hospitals and health centers.

Reference

Kershaw TS, Magriples U, Westdahl C, Rising SS, Ickovics J. Pregnancy as a window of opportunity for HIV prevention: effects of an HIV intervention delivered within prenatal care. Am J Public Health. 2009 Nov;99(11):2079-86. Epub 2009 Sep 17. PubMed PMID: 19762662.

Psychologists Study New Treatments for Smokers from Underserved Populations

WASHINGTON – With the national trend toward quitting smoking flat, psychologists are finding some success with treatments aimed at helping smokers from underserved groups, including racial and ethnic minorities and those with psychiatric disorders.

In a special section of this month’s issue of the Journal of Consulting and Clinical Psychology, published by the American Psychological Association, researchers report on several effective treatments that may help these smokers in an effort to increase national smoking cessation rates. The percentage of American smokers rose from 19.8 percent in 2007 to 20.6 percent in 2008, after a 10-year steady decline in smoking rates, according to the latest figures from the Centers for Disease Control and Prevention.

“One of the reasons smoking rates have remained stagnant is because these underserved groups of smokers have not been adequately targeted by research and treatment,” said the special section editor, Belinda Borrelli, PhD, who is with the Centers for Behavioral and Preventive Medicine at Brown University Medical School. Underserved smokers include those who have a 10 percent higher smoking rate than the general population, have less access to treatments, and are more likely to be excluded from long-term treatments trials, according to Borelli.

In one article, researchers found that success in stopping smoking differed for different psychiatric disorders. For example, compared to smokers with no psychiatric disorders, smokers who had an anxiety disorder were less likely to quit smoking six months after treatment.

In the same article, researchers found that people’s barriers to quitting were directly related to what type of psychiatric disorder they had. For example, smokers who had ever been diagnosed with an anxiety disorder reported a strong emotional bond with their cigarettes while smokers ever diagnosed with a substance use disorder reported that social and environmental influences were especially likely to affect their smoking. “This information may help clinicians gauge relapse risk and identify treatment targets among smokers who have ever had psychological illnesses,” said lead author Megan Piper, PhD, from the University of Wisconsin School of Medicine and Public Health.

Evidence-based smoking cessation treatments are addressed in another article in this special section. Researchers from the University of Miami looked at the effect of intensive cognitive-behavioral therapy on African-American smokers. They placed 154 African-American smokers wearing nicotine patches into one of two six-session interventions. Participants in the group using cognitive-behavioral techniques were taught relapse prevention strategies and coping skills, along with other techniques. The other group participated in a health education series that explained general medical conditions that are associated with smoking, such as heart disease and lung cancer.

Compared with general health education, participation in cognitive-behavioral therapy sessions more than doubled the rate of quitting at a six month follow-up, from 14 percent to 31 percent the researchers found. “We know cognitive-behavioral therapy helps people quit, but few studies have examined this treatment’s effect on African-American smokers,” said the study’s lead author, Monica Webb, PhD, of the University of Miami. “Hopefully, our findings will encourage smoking cessation counselors and researchers to utilize cognitive-behavioral interventions in this underserved population.”

Borrelli, the section editor, examined another minority group—Latinos. She measured the amount of second-hand smoke in participants’ homes and gave feedback to smokers about how much smoke their child with asthma was exposed to. For example, they were told that their child was exposed to as much smoke as if the child smoked ‘x’ number of cigarettes him- or herself during the week of the measurement – this was the experimental group. Smokers in the control group underwent standard cognitive-behavioral treatment for smoking cessation. Smokers in the experimental group were twice as likely to quit as the control group, Borrelli found. “The child’s asthma problems may provide a teachable moment for parents whereby they become more open to the smoking cessation messages,” Borrelli said. “Providing treatment that is focused on the health needs of the family, and delivered in a culturally tailored manner, has the potential to address health care disparities for Latino families.”

Special Section: “Smoking Cessation – Innovative Treatments and Understudied Populations,” Section Editor: Belinda Borrelli, PhD, Brown University Medical School and Miriam Hospital; Journal of Consulting and Clinical Psychology, Vol. 78, No. 1.

Contact Dr. Belinda Borrelli by e-mail or her phone number is (401) 741-7994.

Exciting new activities may help prevent relapse

Researchers Evaluated Intervention Focusing on Preventive Health and Future Goal Attainment, Not Moral Choices

Teens who received a behavioral intervention centered on abstinence were more likely to delay first sexual contact than teens who received a control intervention focusing on general health promotion, according to an NIMH-funded study. Though differing from federally funded abstinence-only programs, the researchers describe how an abstinence-based intervention may help delay sexual activity among adolescents in the February 2010 issue of the Archives of Pediatrics and Adolescent Medicine.

Background

Sexually active teens face a broad range of potentially negative outcomes related to HIV and other sexually transmitted infections (STIs) and unplanned pregnancies. In particular, African American teens experience these outcomes at much higher rates than their peers.^1,2,3,4

Studies have shown that behavioral interventions can reduce behaviors related to HIV/STI risk. However, U.S. policymakers do not agree on which type of intervention is most appropriate or most effective for use with teens. Many states have adopted abstinence-only programs in their school systems, which not only lack adequate research showing their efficacy, but have been criticized for inclusion of inaccurate information, negative portrayal of sex, and a moralistic tone.

To address this issue, John B. Jemmott, III, Ph.D., of the University of Pennsylvania, and colleagues recruited 662 students in grades 6 and 7 (ages 10—15) from four, public middle schools serving low-income, African American, urban communities. They were randomly assigned to one of five behavioral interventions:

• Abstinence—based-designed to strengthen beliefs supporting abstinence (e.g., prevent pregnancy and STIs, foster attainment of future goals) and increase skills for resisting pressure to have sex. In addition, the intervention providers were expressly instructed not to discredit use of condoms and to correct false beliefs about the effectiveness of condoms in preventing STIs.
• Safer sex—designed to strengthen beliefs supporting condom use and increase skills to negotiate condom use and use condoms properly.
• 12-hour comprehensive—combined the design and aims of the abstinence-based and safer sex interventions.
• 8-hour comprehensive—provided an abbreviated version of the 12-hour comprehensive intervention. This allowed the researchers to assess whether any benefits of the longer comprehensive intervention could be attributed to the students spending more time in the intervention.
• Health promotion—designed to increase knowledge and motivation regarding general healthful behaviors, such as following a balanced diet and discouraging cigarette smoking. This intervention served as the control condition.

All interventions were designed to increase knowledge about HIV and STIs except for the health promotion intervention. Four of the interventions were provided over two 4-hour weekend sessions (eight hours total). The 12-hour comprehensive intervention was provided over three 4-hour weekend sessions. Participants completed questionnaires at the start of the study, immediately after the last intervention session, and every three months afterwards for up to two years.

In addition, the researchers tested an intervention maintenance program. This program, which was tested in half of the participants, consisted of two 3-hour booster sessions given at six weeks and three months after completion of the initial intervention; six issues of a newsletter; and six brief, one-on-one counseling sessions with the original facilitator provided over a 21-month period.

Results of the Study

At the study’s outset, 23.4 percent of the teens reported that they were already sexually active.

At the two-year follow-up, students who received the abstinence-based intervention and had not been sexually active at the study’s outset were significantly less likely to have initiated sexual activity (33 percent) or to have recently had sex (20 percent) compared to the those who received the health promotion intervention; among students in the control group with no prior sexual activity, 49 percent reported first sexual contact and 29 percent recently had sex. None of the other interventions had a significant effect on the initiation of sexual activity when compared to the control condition. The researchers did not compare the four HIV-prevention interventions with each other on any outcome measures.

Students who received either the 8-hour or 12-hour comprehensive intervention were significantly less likely to report having multiple partners (about 9 percent in each group) than those in the control group (14 percent).

The intervention maintenance program modestly enhanced the effectiveness of the abstinence-based and 12-hour comprehensive interventions at reducing multiple partners, but showed no other benefits.

None of the interventions significantly affected consistent condom use.

Significance

According to the researchers, their study shows that a theory-based, abstinence-only intervention may be an effective method for delaying sexual initiation in middle school students who are not already sexually active. They also emphasized that the abstinence-based intervention used in this study was not designed to meet federal criteria for abstinence-only programs. Thus, it is not subject to the criticisms those programs face. Similarly, the results of the abstinence-based intervention cannot be generalized to all abstinence programs or to all populations.

Also of note, the study did not support a common concern about abstinence-only interventions—that they reduce the likelihood of condom use among teens. Similarly, the other behavioral interventions did not increase sexual activity when compared to the control group, a concern expressed by some regarding comprehensive sex education interventions.

The researchers further cautioned that their findings do not suggest that this or other abstinence-based interventions are the best approach for all adolescents. However, the use of evidence-based abstinence interventions may be an effective means of delaying sexual initiation in some communities for whom abstinence is the only acceptable approach to sex education.

What’s Next

Further work is needed to determine whether the interventions assessed in this study are effective for other teen populations and to determine when they affect biological outcomes such as STI or pregnancy rates. Different methods may be more effective in addressing the specific needs of older youth or teens in committed relationships, for example. The researchers also expressed the need for additional studies to identify ways of prolonging the effectiveness of HIV/STI interventions.

Reference

Jemmott JB, Jemmott LS, Fong GT. Efficacy of a Theory-Based Abstinence-Only Intervention over 24 Months: A Randomized Controlled Trial with Young Adolescents. Arch Pediatr Adolesc Med. 2010 Feb;164(2):152-9.

¹ Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2006. Atlanta, GA: Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, November 2007. Downloaded February 22. 2008 at http://www.cdc.gov/std/.

² Centers for Disease Control and Prevention. HIV/AIDS surveillance in adolescents and young adults (through 2005). Atlanta, GA: Division of HIV/AIDS, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, October 23, 2007. Downloaded February 19, 2008 at www.cdc.gov/hiv/topics/surveillance/resources/slides/adolescents/index.htm.

³ Miller WC, Ford CA, Morris M, Handcock MS, Schmitz, JL, Hobbs MM, Cohen MS, Harris KM, Udry JR. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA. 2004;291:2229-2236.

⁴ Ventura SJ, Abma JC, Mosher WD, Henshaw SK. Recent trends in teenage pregnancy in the United States, 1990-2002. Health E-Stats. Hyattsville, MD: National Center for Health Statistics. Released December 2006. Downloaded June 6, 2007 at http://www.csctulsa.org/images/Teen%20Pregnancy%20Trends%201990-2002.pdf

Amidst the background hum of electrical signaling generated by neurons in the brain, scientists have found that local groups of neurons, firing in coordination, sometimes create a signal that is mirrored instantaneously and precisely by other groups of neurons across the brain.  These transient episodes of coherence across different parts of the brain may be an electrical signature of thought and actions.

Background

One of the goals of neuroscience research is to identify how thoughts and actions are encoded in the activity of neurons.  A challenge has been to extract meaningful patterns from the ongoing tumult of electrical activity in the brain.  This global electrical activity is built from the firing of individual neurons.  A single neuron responds to a stimulus in an all or nothing manner—if the stimulus reaches a certain threshold, the neuron “fires” an electrical signal.  Groups of neurons firing in a coordinated way create a local electrical field that is in itself a signal that can vary in pattern.  These local field potentials (LFPs) have been a target of research.

This Study

In this research, Dietmar Plenz and colleagues at NIMH and Duke University pinpointed LFPs in the cortex that surpassed a minimal size threshold, and then searched the rest of the cortex to see what was occurring at the same time.  In each case, they found other answering LFPs across the brain that mimicked each other with high precision: there was no degradation or loss of power (amplitude) in the signal.  Unlike what is observed after dropping a stone in a pond—with wavelets getting smaller farther from the stone—the intensity of the LFPs was the same across the brain.  The investigators call these LFPs coherence potentials.  Although LFPs that occur during these transient episodes of coherence are identical to each other, they are also multidimensional and potentially infinitely diverse, providing a means to encode information.  Most LFPs do not reach the threshold that characterizes a coherence potential but with those that do, propagation of the LFPs across the brain is extraordinarily rapid.  The authors note that the rapid dispersion of such a signal mimics the spread of ideas and behaviors in social networks; a sufficiently provocative idea can spread very swiftly through a population.

Significance

Coherence potentials simultaneously engage groups of neurons in different parts of the brain with diverse functions.  This is consistent with the multi-faceted nature of mental associations and memories—a memory focused on a person or object might conjure various kinds of sensations and thoughts—visual, tactile, auditory, and emotional, for example.

These findings emerged from recent work that demonstrated that, like other systems in nature, the cortex exists at a critical state between stability and instability.  A characteristic of this state in the brain is the presence of neuronal avalanches—if a stimulus reaches a certain threshold, it will set off cascades of neuronal firing.  This dynamic is analogous to when the slope of a sandpile reaches a point at which adding one more grain will trigger an avalanche.  The adherence of the cortex to this critical state ensures that the brain can respond to a wide range of stimuli, but not lapse into a chaos of excess activity (such as the too-synchronous firing during epilepsy).  Coherence potentials emerge predominantly when the cortex is critical, that is, when it displays neuronal avalanches.  Nudging the cortex away from this point, by inhibiting neuronal signaling with medications for example, disrupts these dynamical patterns.

What’s Next

Coherence potentials were present in cells in culture as well as awake monkeys, a robust demonstration that they occur in the functioning cortex.  Future studies will be aimed at monitoring coherence potentials in the context of behavioral function with the ultimate aim of making a connection between specific coherence potentials and behaviors.

Reference

Thiagarajan, T.C., Lebedev, M.A., Nicolelis, M.A., and Plenz, D. Coherence potentials: loss-less, all-or-none network events in the cortex.  PLoS Biology 2010, doi:10.1371/journal.pbio.1000278.

Increased Risk May Stem From Variation in Gene On/Off Switch

Researchers, for the first time, have pinpointed a genetic hotspot that confers risk for both bipolar disorder and depression. People with either of these mood disorders were significantly more likely to have risk versions of genes at this site than healthy controls. One of the genes, which codes for part of a cell’s machinery that tells genes when to turn on and off, was also found to be over-expressed in the executive hub of bipolar patients’ brains, making it a prime suspect. The results add to mounting evidence that major mental disorders overlap at the molecular level.

“People who carry the risk versions may differ in some dimension of brain development that may increase risk for mood disorders later in life,” explained Francis McMahon, M.D., of the NIMH Mood and Anxiety Disorders Program, who led the study.

McMahon and an international team of investigators, supported, in part by NIMH, report on the findings of their genome-wide meta-analysis online January 17, 2010 in the journal Nature Genetics.

Background

Major mood disorders affect 20 percent of the population and are among the leading causes of disability worldwide. It’s long been known that bipolar disorder and unipolar depression often run together in the same families, hinting at some shared lineage. Yet, until now, no common genes or chromosomal locations had been identified.

McMahon and colleagues analyzed data from five different genome-wide association studies (GWAS) totaling more than 13,600 people, and confirmed their results in 3 additional independent samples totaling 4,677 people.

Findings of This Study

Genetic variations on Chromosome 3 were significantly associated with both mood disorders. The suspect gene, called PBRM1, codes for a protein critical for chromatin remodeling, a key process in regulating gene expression. A neighboring gene is involved in the proliferation of brain stem cells.

The researchers pinpointed a “protective” version of the PBRM1 gene that is carried by 41 percent of healthy controls, but only 38 percent of people with bipolar and unipolar depression. The risk version was found in 62 percent of mood disorder cases and 59 percent of controls. The researchers also showed that PBRM1 is expressed more in the prefrontal cortex of people with bipolar disorder than in controls.

Significance

Since mood disorders likely involve altered gene expression during brain development and in response to stress, PBRM1’s profile makes it a good potential candidate gene. This first genetic evidence of unipolar/bipolar overlap is also the first significant genome-wide association with any psychiatric illness in the Chromosome 3p region.

However, the findings underscore limitations of the GWAS approach, which looks for connections to gene versions that are common in the population. Having one copy of this risk variant increases vulnerability for developing a mood disorder by a modest 15 percent. Why do some people with this variant — and presumably other, yet to be discovered, shared risk genes — develop bipolar disorder while others develop unipolar depression or remain healthy? Environmental influences and epigenetic factors may be involved, suggest the researchers, who note that “genetic association findings so far seem to account for little of the inherited risk for mood disorders.”

“Our results support the growing view that there aren’t common genes with large effects that confer increased risk for mood disorders,” said McMahon. “If there were, in this largest sample to date, we would have found them. The disorders likely involve many genes with small effects — and different genes in different families — complicating the search. Rarer genes with large effects may also exist.”

What’s Next?

Ultimately, findings such as these may lead to identification of common biological pathways that may play a role in both unipolar and bipolar illness and suggest strategies for better treatment, said McMahon. The results add to other evidence of overlap that is spurring a new NIMH initiative to make sense of research findings that don’t fit neatly into current diagnostic categories. See: Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research.

Bipolar disorder and unipolar depression often run in the same families, as this pedigree diagram illustrates. The new study is the first to trace both illnesses to a shared chromosomal hotspot.

Source: NIMH Genetics Initiative Bipolar Disorder Consortium

Reference

Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.the Bipolar Disorder Genome Study (BiGS) Consortium, McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD, Steele CJ, Breuer R, Strohmaier J, Wendland JR, Mattheisen M, Mühleisen TW, Maier W, Nöthen MM, Cichon S, Farmer A, Vincent JB, Holsboer F, Preisig M, Rietschel M. Nat Genet. 2010 Jan 17. [Epub ahead of print]PMID: 20081856

Samples included in the meta-analysis:

dbGaP National Institute of Mental Health bipolar disorder
Genetic Association Information Network MDD
Wellcome Trust Case Control Consortium
German sample
Systematic Treatment Enhancement Program for Bipolar Disorder