Out of sync with the world: Body clocks of depressed people are altered at cell level

Finding of disrupted brain gene orchestration gives first direct evidence of circadian rhythm changes in depressed brains, opens door to better treatment ANN ARBOR, Mich. — Every cell in our bodies runs on a 24-hour clock, tuned to the night-day, light-dark cycles that have ruled us since the dawn of humanity. The brain acts as timekeeper, keeping the cellular clock in sync with the outside world so that it can govern our appetites, sleep, moods and much more. But new research shows that the clock may be broken in the brains of people with depression -- even at the level of the gene activity inside their brain cells. It's the first direct evidence of altered circadian rhythms in the brain of people with depression, and shows that they operate out of sync with the usual ingrained daily cycle. The findings, in the Proceedings of the National Academy of Sciences, come from scientists from the University of Michigan Medical School and other institutions. The discovery was made by sifting through massive amounts of data gleaned from donated brains of depressed and non-depressed people. With further research, the findings could lead to more precise diagnosis and treatment for a condition that affects more than 350 million people worldwide. What's more, the research also reveals a previously unknown daily rhythm to the activity of many genes across many areas of the brain – expanding the sense of how crucial our master clock is professional counselor continuing education In a normal brain, the pattern of gene activity at a given time of the day is so distinctive that the authors could use it to accurately estimate the hour of death of the brain donor, suggesting that studying this "stopped clock" could conceivably be useful in forensics. By contrast, in severely depressed patients, the circadian clock was so disrupted that a patient's "day" pattern of gene activity could look like a "night" pattern -- and vice versa. The work was funded in large part by the Pritzker Neuropsychiatric Disorders Research Fund, and involved researchers from the University of Michigan, University of California's Irvine and Davis campuses, Weill Cornell Medical College, the Hudson Alpha Institute for Biotechnology, and Stanford University. The team uses material from donated brains obtained shortly after death, along with extensive clinical information about the individual. Numerous regions of each brain are dissected by hand or even with lasers that can capture more specialized cell types, then analyzed to measure gene activity. The resulting flood of information is picked apart with advanced data-mining tools. Lead author Jun Li, Ph.D., an assistant professor in the U-M Department of Human Genetics, describes how this approach allowed the team to accurately back-predict the hour of the day when each non-depressed individual died – literally plotting them out on a 24-hour clock by noting which genes were active at the time they died. They looked at 12,000 gene transcripts isolated from six regions of 55 brains from people who did not have depression. This provided a detailed understanding of how gene activity varied throughout the day in the brain regions studied. But when the team tried to do the same in the brains of 34 depressed individuals, the gene activity was off by hours. The cells looked as if it were an entirely different time of day. "There really was a moment of discovery," says Li, who led the analysis of the massive amount of data generated by the rest of the team and is a research assistant professor in U-M's Department of Computational Medicine at Bioinformatics. "It was when we realized that many of the genes that show 24-hour cycles in the normal individuals were well-known circadian rhythm genes – and when we saw that the people with depression were not synchronized to the usual solar day in terms of this gene activity. It's as if they were living in a different time zone than the one they died in." Huda Akil, Ph.D., the co-director of the U-M Molecular & Behavioral Neuroscience Institute and co-director of the U-M site of the Pritzker Neuropsychiatric Disorders Research Consortium, notes that the findings go beyond previous research on circadian rhythms, using animals or human skin cells, which were more easily accessible than human brain tissues. "Hundreds of new genes that are very sensitive to circadian rhythms emerged from this research -- not just the primary clock genes that have been studied in animals or cell cultures, but other genes whose activity rises and falls throughout the day," she says. "We were truly able to watch the daily rhythm play out in a symphony of biological activity, by studying where the clock had stopped at the time of death. And then, in depressed people, we could see how this was disrupted." Now, she adds, scientists must use this information to help find new ways to predict depression, fine-tune treatment for each depressed patient, and even find new medications or other types of treatment to develop and test. One possibility, she notes, could be to identify biomarkers for depression – telltale molecules that can be detected in blood, skin or hair. And, the challenge of determining why the circadian clock is altered in depression still remains. "We can only glimpse the possibility that the disruption seen in depression may have more than one cause. We need to learn more about whether something in the nature of the clock itself is affected, because if you could fix the clock you might be able to help people get better," Akil notes. The team continues to mine their data for new findings, and to probe additional brains as they are donated and dissected. The high quality of the brains, and the data gathered about how their donors lived and died, is essential to the project, Akil says. Even the pH level of the tissue, which can be affected by the dying process and the time between death and freezing tissue for research, can affect the results. The team also will have access to blood and hair samples from new donors. ### The researchers note that the Pritzker funding in combination with federal research funding made it possible for the scientists to study this issue in an exploratory way. The research was historically funded by a Conte Center grant from the National Institute of Mental Health, and partly funded by the William Lion Penzner Foundation, the Della Martin Foundation, the Office of Naval Research (N00014-09-1-059 and N00014-12-1-0366), the National Alliance for Research on Schizophrenia and Depression's Abramson Family Foundation Investigator Award, and an International Mental Health Research Organization – Johnson & Johnson Rising Star Translational Research Award. In addition to Li and Akil, the study's authors are Blynn G. Bunney, Fan Meng, Megan H. Hagenauer, David M. Walsh, Marquis P. Vawter, Simon J. Evans, Prabakhara V. Choudary, Preston Cartagena, Jack D. Barchas, Alan F. Schatzberg, the late Edward G. Jones, Richard M. Myers, U-M MBNI co-director Stanley J. Watson, Jr., and William E. Bunney. Reference: PNAS Early Edition, http://www.pnas.org/cgi/doi/10.1073/pnas.1305814110

Surprising Rate of Women Have Depression After Childbirth

One in every seven women have significant depressive symptoms March 13, 2013 | by Marla Paul CHICAGO --- A surprisingly high number of women have postpartum depressive symptoms, according to a new, large-scale study by a Northwestern Medicine® researcher. This is the largest scale depression screening of postpartum women and the first time a full psychiatric assessment has been done in a study of postpartum women who screened positive for depression Depressive Disorders CE Course The study, which included a depression screening of 10,000 women who had recently delivered infants at single obstetrical hospital, revealed a large percentage of women who suffered recurrent episodes of major depression. The study underscored the importance of prenatal as well as postpartum screening. Mothers’ and infants’ health and lives hang in the balance. The lives of several women who were suicidal when staff members called them for the screening were saved likely as a result of the study’s screening and immediate intervention. “In the U.S., the vast majority of postpartum women with depression are not identified or treated even though they are at higher risk for psychiatric disorders,” said Northwestern Medicine lead study author Katherine L. Wisner, M.D. “It’s a huge public health problem. A woman’s mental health has a profound effect on fetal development as well as her child’s physical and emotional development.” Wisner is director of Northwestern’s Asher Center for the Study and Treatment of Depressive Disorders and the Norman and Helen Asher Professor of Psychiatry and Behavioral Sciences and professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine. She’s also a physician at Northwestern Memorial Hospital. “A lot of women do not understand what is happening to them,” Wisner said. “They think they’re just stressed or they believe it is how having a baby is supposed to feel.” The paper was be published in JAMA Psychiatry March 13. Wisner conducted the research when she was at the University of Pittsburgh. In the study, 14 percent of the women screened positive for depression. Of that group, 826 received full psychiatric assessments during at-home visits. Some of the key findings from those assessments: - In women who screened positive for depression, 19.3 percent thought of harming themselves. “Most of these women would not have been screened and therefore would not have been identified as seriously at risk,” Wisner said. “We believe screening will save lives.” Suicide accounts for about 20 percent of postpartum deaths and is the second most common cause of mortality in postpartum women. - Many women who screened positive for major depression postpartum had already experienced at least one episode of depression previously and, in addition, had an anxiety disorder. The study found 30 percent of women had depression onset prior to pregnancy, 40 percent postpartum and 30 percent during pregnancy. More than two-thirds of these women also had an anxiety disorder. “Clinicians need to know that the most common clinical presentation in the post-birth period is more complex than a single episode of depression,” Wisner said. “The depression is recurrent and superimposed on an anxiety disorder.“ - Of the women who screened positive for major depression, 22 percent had bipolar disorder, the majority of whom had not been diagnosed by their physicians. There is often a delay in correctly diagnosing bipolar disorder, which depends on identifying not only the depressed phase but the manic or hypomanic phase as well. But postpartum is the highest risk period for new episodes of mania in a woman’s life. “That’s a very high rate of bipolar disorder that has never been reported in a population screened for postpartum depression before,” said Wisner. “It is significant because antidepressant drug treatment alone can worsen the course of bipolar disorder.” In addition, women who have been pregnant in the past year are less likely to seek treatment for depression than women who have not been pregnant, previous research has shown. Maximizing a woman’s overall mental and physical health in pregnancy and after childbirth is critically important. “Depression during pregnancy increases the risk to a woman and her fetus,” Wisner said. “Depression is a physiological dysregulation disorder of the entire body.” Maternal prenatal stress and depression is linked to preterm birth and low infant birth weight, which increases the risk of cardiovascular disease. Depression also affects a woman’s appetite, nutrition and prenatal care and is associated with increased alcohol and drug use. Women with untreated depression have a higher body mass index preconception, which carries additional risks. When a new mother is depressed, her emotional state can interfere with child development and increases the rate of insecure attachment and poor cognitive performance of her child, Wisner said. Screening prenatal and postpartum are essential (Illinois requires mandatory screening for perinatal mental health disorders), but the health care field must develop cost effective and accessible treatment, Wisner emphasized. “If we identify patients we must have treatment to offer them,” Wisner said. The study was funded by grant RO1 MH 071825 from the National Institute of Mental Health of the National Institutes of Health.

Bipolar Disorder In Children: Why Are The Rates Rising?

Bipolar Disorder In Children: Why Are The Rates Rising?
By Michael F. Hogan, PhD, Commissioner, New York State Office of Mental Health; and
Lloyd I. Sederer, M.D., Medical Director, New York State Office of Mental Health

Recent media reports tell us that the diagnosis of bipolar disorder in children and adolescents (formerly called manic depressive disorder) is forty times more frequent than it was just ten years ago. Can the numbers of children and adolescents with this illness increase so rapidly? Are medications being over-prescribed?

The rapid increase in diagnoses in such a short period of time cannot be explained by changes in genetics, environment or families. In part it must be due to a broader definition of the illness, which now includes anger and hyperactivity.

But the signs and symptoms needed to make the diagnosis of bipolar disorder, according to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM IV) have not changed in recent years. Diagnoses are being made more liberally, perhaps to the benefit of some children but clearly also to the detriment of others.

For a reliable diagnosis to be made, symptoms common in this disorder such as mood swings, irritability and impulsive behavior must occur during a distinct period of a mood disturbance, a hallmark of this illness and the DSM IV definition. Many children are impulsive and irritable, but that in itself does not meet the criteria for this illness. These symptoms occur with other disorders found in children and adolescents, such as attention deficit hyperactivity disorder (ADHD), depression with agitation and irritability, conduct disorder, and substance use disorders.

A diagnosis of bipolar disorder in children and adolescents does not tell us if the childhood form of the illness will continue into adulthood. Many children with mood swings, depression, and irritability have been brought to physicians over many years. They have been diagnosed with various disorders, including ADHD, conduct disorder and depression, according to the trends at the time. Diagnoses made today may change for individual children as they age, and for children in the future as psychiatry matures.

What should psychiatrists do now? What should parents and caretakers expect in the treatment of their children? A heightened awareness of the existence of bipolar disorder in children may be beneficial if it helps us to recognize more cases of true bipolar disorder and institute treatment earlier. It can also cause confusion and concern in parents and psychiatrists around the use of the medications prescribed for bipolar disorder.

First, a child should be assessed directly by a child and adolescent psychiatrist with information obtained from parents, caregivers and sometimes teachers. Second, valid rating scales can help introduce some objectivity to what is still a professional judgement. The Mood Disorder Questionnaire and the Young Mania Rating Scale are specific to bipolar disorder. Scales such as the Conners’ (with parent and teacher rating forms) for hyperactivity and ADHD can help to differentiate these common conditions, even if many children and adolescents with bipolar disorder also have ADHD. The Beck Depression Inventory (children’s version) can help identify depression. Third, as noted earlier, a consultation or second opinion is another important way to confirm or refute a diagnosis made by one doctor. This is especially valuable in children whose behaviors stimulate desperate efforts to “do something.” Any doctor not open to a second opinion should be suspect.

The treatment of bipolar disorder in children and adolescents, or any mental disorder for that matter, begins with forming a trusting relationship with the child and parents. This means the physician should provide information and educate the family about mental illness, be open to questions and concerns, and share decision-making. Benefits, risks and side-effects of any treatment must be offered in a clear and understandable manner; if you as a parent or youth do not understand, say so and expect a good answer.

Medications are a primary treatment for bipolar disorder and many mental illnesses, and they can provide invaluable help. But medications are only one form of intervention, and not enough in themselves. Various forms of psychotherapy in association with medication may be helpful. In particular, “psycho-educational treatment” for the child and parents provides concrete information about the illness, its impact, and treatment options. Cognitive behavior therapy can be especially helpful in the depressive phase of bipolar disorder and is effective in reducing disruptive behaviors. Support groups for families of children and adolescents with bipolar disorder and other severe disorders also can be helpful.

In light of the rise in diagnosis of this disorder, doctors, families and youth have reason to be concerned that a diagnosis is accurate and the treatment it leads to is optimal. Families should insist on clear information, seek second opinions when unsure, and demand monitoring of care to see if the diagnosis “holds” over time. Parents and youth should expect careful observation of any prescribed medications, and recognize that medications may be a critical part of the treatment but they are not sufficient when it comes to the care of our children.

Women and Depression Fast Facts

For more information and ceus ceu's continuing education regarding depression, click link below

online mft ceus

Women and Depression Fast Facts
One in four women will experience severe depression at some point in life.

Depression affects twice as many women as men, regardless of racial and ethnic background or income.

Depression is the number one cause of disability in women.

In general, married women experience more depression than single women do, and depression is common among young mothers who stay at home full-time with small children.

Women who are victims of sexual and physical abuse are at much greater risk for depression.

At least 90 percent of all cases of eating disorders occur in women, and there is a strong relationship between eating disorders and depression.

Depression can put women at risk for suicide. While more men than women die from suicide, women attempt suicide about twice as often as men do.

Only about one-fifth of all women who suffer from depression seek treatment.

Depression can - and should - be treated.
For more information, contact:
SAMHSA's National Mental Health Information Center
800-789-2647
mentalhealth.samhsa.gov
11/21/00

Resources

American Psychological Association
750 First Street, NE
Washington, DC 20002-4242
202-336-5500 or 800-374-2721
www.apa.org


National Alliance for the Mentally Ill
Colonial Place Three
2107 Wilson Boulevard, Suite 300
Arlington, VA 22201-3042
703-524-7600 or 800-950-6264
www.nami.org


National Asian Women's Health Organization
250 Montgomery Street, Suite 900
San Francisco, CA 94104
415-989-9747
www.nawho.org


National Institute of Mental Health
6001 Executive Boulevard
Room 8184, MSC 9663
Bethesda, MD 20892-9663
301-443-4513 or 800-421-4211
www.nimh.nih.gov


National Mental Health Association
2001 N. Beauregard Street - 12th Floor
Alexandria, VA 22311
703-684-7722 or 800-969-6642
www.nmha.org


Society for Women's Health Research
1828 L Street, NW, Suite 625
Washington, DC 20036
202-223-8224
www.womens-health.org


The National Women's Health Information Center
A service of the Office on Women's Health in the
U.S. Department of Health and Human Services
800-994-WOMAN
www.WomensHealth.gov