Tegretol (Carbamazepine)

You hear a lot about some of the more popular medications used to treat bipolar disorder, including lithium, Depakote, and Lamictal, but one medication that seems to be less common is Tegretol (Carbamazepine).

According to Dr. Fink, “Tegretol is used far less often than Depakote – for no particular reason it seems other than habit on the part of physicians.”

Dr. Fink has quite a bit to say about Tegretol and has recently shared her insights on the Bipolar Beat in her post entitled “Bipolar Disorder Medication Spotlight: Tegretol (Carbamazepine).”

Developing a New Antidepressant

Current use of antidepressants has been a mixed bag – sometimes they work and sometimes not.

Large multicenter studies such as STAR*D have discovered that current antidepressant medications are effective, but not as effective as one might hope. Thus, there is a significant need for new treatment mechanisms for depression.

On that front, there has been mixed news as well. One of the most exciting new drugs to reach human clinical trials, one that blocks the corticotrophin releasing factor-1 (CRF1) receptor, did not work in a large clinical trial sponsored by Pfizer Pharmaceuticals.

Is it time to abandon CRF1 antagonists as antidepressants or should we revisit these agents from a new perspective?

It is in this context that a new paper by Alexandre Surget and colleagues, published in issue of Biological Psychiatry, is particularly interesting.

Through prior work, it has been shown that the ability to reverse the stress-related disruption of hippocampal neurogenesis, the ability of the brain to make new nerve cells in adulthood, was important to the actions of our available antidepressant medications.

In this new study, the researchers affirm the prior findings, but suggest that two experimental approaches to the treatment of depression, blockade of the CRF1 receptor or the vasopressin-1B (V1B) receptor, retain their efficacy in reversing the impact of stress on behavior even when neurogenesis is disrupted.

Catherine Belzung, Ph.D., corresponding author on this article, further explains that “we now report evidence that restoration of the functioning of the stress axis may be the key to how these new antidepressant approaches might work.”

How can one reconcile these interesting research findings in animals with the lack of antidepressant efficacy of a CRF1 receptor antagonist in the Pfizer study? Is this approach simply ineffective in humans or might there be subgroups of patients who might be more likely to respond to a CRF1 antagonist?

The Surget et al. data raise the possibility that CRF1 receptor antagonists might be effective in treating stress-related behavioral disturbances even in a context where other antidepressants do not work, perhaps due to disruption of neurogenesis.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments:

“These findings lend weight to the hope that CRF1 antagonists might play a role in the treatment of antidepressant-resistant symptoms of depression or posttraumatic stress disorder. If so, CRF1 antagonists could fulfill an important unmet need.”

He adds that “we do not need another Prozac, but we urgently need to find ways to help the large number of patients who fail to respond adequately to our available treatments.”

Source: Elsevier

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Chronic Stress Genetically Alters Immune System

The link between stress and illness has been hypothesized for decades. Most people would agree that stress increases your risk for illness and this is particularly true for severe long-term stresses, such as caring for a family member with a chronic medical illness.

However, we still have a relatively limited understanding of exactly how stress contributes to the risk for illness.

A recent issue of Biological Psychiatry sheds new light on one link between stress and illness by describing a mechanism through which stress alters immune function.

In a very promising preliminary study, Miller and colleagues found that the pattern of gene expression differed between caregivers of family members with cancer relative to a matched group of individuals who did not have this type of life stress.

They found that among the caregivers, even though they had normal cortisol levels in their blood, the pattern of gene expression in the monocytes, a type of white blood cell involved in the body’s immune response, was altered so that they were relatively less responsive to the anti-inflammatory actions of cortisol, but relatively more responsive to pro-inflammatory actions of a transcription factor called nuclear factor-kappa B, or NF-κB.

Gregory Miller, Ph.D., corresponding author, explains more simply that, although “caregivers have similar cortisol levels as controls, their cells seem to be ‘hearing’ less of this signal.

In other words, something goes awry in caregivers’ white blood cells so they are not able to ‘receive’ the signal from cortisol that tells them to shut down inflammation.”

Thus, the current findings might help to explain why the caregivers would seem to be in a chronic pro-inflammatory state, a condition of immunologic activation. This activated state could contribute to the risk for a number of medical illnesses, such as depression, heart disease, and diabetes.

Dr. Miller remarks that part of the importance of these findings is “because people have traditionally thought that higher cortisol is the reason that stress contributes to disease, but this work shows that, at least in caregivers, it’s actually the opposite - there’s too little cortisol signal being heard by the cells, rather than too much.”

However, many important related questions still remain unanswered, as noted by John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System.

He comments that in addition to not knowing how stress produces these altered patterns of gene expression in the immune system, “we don’t know how to account for the resilience of some stressed people exposed to severe sustained stress or the vulnerability of some people to relatively mild stress.”

He adds that “the better that we understand the underlying molecular mechanisms that link stress to illness, the more likely we are to make progress in answering these important questions,” and this article is certainly a vital step in that direction.

Source: Elsevier

Verbal Criticism Is Long-Lasting

We all know the famous saying: “Sticks and stones may break my bones, but words will never hurt me,” but is this proverb actually true?

According to some researchers, words may pack a harder punch that we realize.

Psychologists Zhansheng Chen and Kipling D. Williams of Purdue University, Julie Fitness of Macquarie University, and Nicola C. Newton of the University of New South Wales found that the pain of physical events may fade with time, while the pain of social occurrences can be re-instantiated through memory retrievals.

The researchers set up four experiments to demonstrate this finding. In the first two experiments, participants reported the amount of pain they felt while trying to relive a physically or a socially painful experience. After writing detailed accounts of each experience, the participants reported how they felt.

The last two experiments were similar to the first two, except participants were asked to work on some cognitive tasks with different levels of difficulty after reliving a socially or physically painful event.

The results, published in the August issue of Psychological Science, a journal of the Association for Psychological Science, are clear.

Participants who had to recall a socially painful experience reported stronger feelings of pain and relived the experience more intensely than those who had to recall a physically painful event. Furthermore, participants who only had to recall a physically painful event performed better on the difficult mental tasks in comparison to those who had to relive a socially painful event.

A possible explanation for these results could be the evolution of the human brain, specifically in an area called the cerebral cortex, which is responsible for complex thinking, perception and language processing.

“The evolution of the cerebral cortex certainly improved the ability of human beings to create and adapt; to function in and with groups, communities, and culture; and to respond to pain associated with social interactions,” the authors wrote.

“However, the cerebral cortex may also have had an unintended effect of allowing humans to relive, re-experience, and suffer from social pain.”

Source: Association for Psychological Science

Brain Scans Show Depression’s Link to Guilt

Scientists report new findings that will improve the understanding of why some people may be more prone to depression than others.

Dr Roland Zahn, a clinical neuroscientist in The University of Manchester’s School of Psychological Sciences, and his colleagues have identified how the brain links knowledge about social behavior with moral sentiments, such as pride and guilt.

The study, carried out at the National Institutes of Neurological Disorders and Stroke in the US with Dr Jordan Grafman, chief of the Cognitive Neuroscience Section, and Dr Jorge Moll, now at the LABS-D’Or Center for Neuroscience in Rio de Janeiro, Brazil, used functional magnetic resonance imaging (fMRI) to scan the brains of 29 healthy individuals while they considered certain social behaviors.

The findings – published in the journal Cerebral Cortex – for the first time chart the regions of the brain that interact to link knowledge about socially appropriate behavior with different moral feelings, depending on the context in which the social behavior occurs.

“During everyday life we constantly evaluate social behavior and this largely affects how we feel about ourselves and other people,” said Dr Zahn.

“But the way we store and use information about our own and other people’s social behavior are not well understood.

“This latest study used functional brain imaging to identify the circuits in the brain that underpin our ability to differentiate social behavior that conforms to our values from behavior that does not.”

The team observed that social behavior not conforming to an individual’s values evoked feelings of anger when carried out by another person or feelings of guilt when the behavior stemmed from the individuals themselves.

The fMRI scans of each volunteer could then be analyzed to see which parts of the brain were activated for the different types of feeling being expressed. Of particular interest to Dr Zahn were the brain scans relating to feelings of guilt, as these have particular relevance to his current work on depression.

“The most distinctive feature of depressive disorders is an exaggerated negative attitude to oneself, which is typically accompanied by feelings of guilt,” he said.

“Now that we understand how the brains of healthy individuals respond to feelings of guilt, we hope to be able to better understand why and where there are differences in brain activity in people suffering from, or prone to, depression.

“The brain region we have identified to be associated with proneness to guilt has been shown to be abnormally active in patients with severe depression in several previous studies, but until now its involvement in guilt had been unknown.”

“By translating these basic cognitive neuroscience insights into clinical research we now have the potential to discover new key functional anatomical characteristics of the brain that may lie behind depressive disorders.

“The results will hopefully make an important contribution to our understanding of the causes of depression that will ultimately allow new approaches to find better treatments and prevention.”

Source: University of Manchester

Adolescent Protective Response to Depression

A new study on adolescent depression following terror attacks, confirms long-held beliefs that show social support is an excellent tonic for depression.

The research paper by Professor Golan Shahar of Ben-Gurion University of the Negev in Beer-Sheva, Israel, and Professor Christopher Henrich of Georgia State University will be published in the upcoming issue of the prestigious Journal of the American Academy of Child and Adolescent Psychiatry.

The Journal article is titled “Social Support Buffers the Effects of Terrorism on Adolescent Depression: Findings from Sderot, Israel.”

The study followed middle school students in the Israeli city of Sderot who have experienced seven years of ongoing terror attacks by Qassam rockets launched from the nearby Gaza Strip. Researchers examined whether higher levels of baseline social support protected the adolescents from adverse psychological effects of exposure to repeated trauma.

Twenty-nine participants were evaluated before and after a five-month period from May to September 2007, when daily rocket attacks from Gaza increased significantly. Both evaluations measured adolescent self-reported depression, social support from family, friends and school in the context of the ongoing rocket attacks. According to Shahar,

“This provided an exceptional and unique opportunity to examine risk and resilience processes in such a heavily burdened population.”

The findings indicate that a strong support system for adolescents could cushion the effects of depression caused by prolonged exposure to rocket attacks.

According to the authors, “These findings highlight the potential importance of community mental health efforts as protective resources in times of traumatic stress. More research on the subject is necessary to determine the extent to which support helps students cope with the difficulties.”

Source: American Associates, Ben-Gurion University of the Negev

Private lilly forum: “olanzapine(zyprexa) induced dementia”

(Source: soulful sepulcher)

Private lilly forum: “olanzapine(zyprexa) induced dementia”

(Source: soulful sepulcher)

Help Defy Depression

Want to help survivors and those grappling with depression? Just a click can help the nonprofit International Foundation for Research and Education on Depression raise $1.5 million from American Express Member Projects’ initiative. Vote now for this positive effort to try and help get the word out about depression and its many effective treatments:

aLive iThrive is a televised concert with artists and leaders publicly discussing depression. aLive will launch the positive depression brand - a color (green - renewal), a symbol (sunflower, seeds for planting in a field of Hope), month (May), and re-emphasize a 1-800 suicide hotline for those in crisis. We will remember those famous and not so famous we have lost and celebrate those that continue to survive. We will share new tools and treatment options.

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