HCV and Depression
March 10, 2010
Question:
"By treating people with antidepressants who are taking interferon for hepatitis are we interfering with halting the virus?"
Charles Raison, MD:
This is a great question that shows a good grasp of immunology. We give people with hepatitis C virus (HCV) infection interferon (IFN)-alpha because, as a proinflammatory cytokine, IFN-alpha activates the immune system to better rid the body of the virus. Many studies suggest that antidepressants reduce inflammatory signaling. If they do this, maybe they interfere with the action of IFN-alpha, which would lead to a terrible irony. People would feel better on an antidepressant but at the price of going through the miseries of IFN-alpha for nothing, or at least a better chance of a bad outcome.
The answer is—unfortunately—that no one knows.1 Our group was involved in planning what would have been a huge study testing this issue. This study was actually designed to show the opposite—that antidepressant pretreatment would improve viral outcomes because people would be more likely to be able to stay on IFN-alpha as a result of improved side-effect burden. We spent the better part of a year working on it, but it was killed at the FDA, and with that the opportunity to perform a really rigorous examination probably vanished for all time.
0 Comment(s) Continue reading...
Five Traits of a Good Clinician
March 3, 2010
Question:
"What traits in us, the clinicians, affect outcomes in our depressed patients?"
Rakesh Jain, MD, MPH:
This is very well thought out question and I welcome the chance to engage in a dialogue with you and our other readers! We clinicians often talk about patient traits that affect depression outcomes, such as length of depression, number of previous episodes, etc. We also often talk about the capabilities of different pharmacologic and nonpharmacologic treatments, such as how quickly do the interventions work, how effective is it, how does it compare to previous therapies, etc. These are, of course, extremely important questions to ask. But, what we tend to under discuss is what about us, the clinicians, as a variable in affecting patient outcomes. What personal traits, habits, and belief systems in us, the clinicians, affect our patients’ outcomes? Do you agree with me that this is often not discussed?
I am certain you have your own opinions on this issue, and I do too. A study by Schattner and colleagues1 examined the issue of which physician traits do patients desire in a ‘good physician.’ Traits patients reported as highly desirable include professional expertise, patience and attentiveness, informing the patient, representing a patient’s interests, being truthful, and respecting the patient’s preferences.
0 Comment(s) Continue reading...
Genetic Contribution in MDD
February 24, 2010
Question:
"What is the extent of genetic contribution in MDD? I thought that it was mostly a stress-induced condition."
Vladimir Maletic, MD:
Major depressive disorder (MDD) is believed to be a product of interaction between several vulnerability genes and environmental adversity (this includes stress, trauma, and also medical illness).1
There are differing opinions about the relative contribution of genes versus environment. Before one broaches the topic of etiopathogenesis, it would be prudent to clarify the definition of MDD as a diagnostic category. Recent research suggests that MDD is not a single biological entity, but rather a grouping of biologically diverse conditions with similar symptomatic manifestations. Therefore, any statement made about the origins of MDD is by necessity probabilistic: it may apply to a significant number of individuals afflicted by MDD, but certainly not to all of them.1
The body of genetic research into origins of MDD would indicate a strong influence of heritability. While estimates of heritability range from 30% to 50%, it is clear that environment has at least an equal, if not greater, contribution.2 Genetic pattern of MDD inheritance is a very complex one. Vulnerability towards MDD is conferred by interactions of multiple different genes with differing magnitude of effect. Estimates vary from dozens of genes with moderate-to-mild effect on one end, to a cumulative impact of thousands of genes with minor individual contributions at the other extreme. Research into MDD genetics is further confounded by complicated gene interactions (a process also known as epistasis): two “vulnerability” genes may have a synergistic effect, amplifying each other’s influence, or their contributions may cancel each other out!1
0 Comment(s) Continue reading...
Bridging the Brain to the Body
February 17, 2010
Question:
"Could you please comment further on the quote you cited by Dr. Charles Mayo and how the concept of the progressive nature of neuropsychiatric illnesses bridges the brain to the body?"
Jon W. Draud, MD, MS:
This is an excellent question that gets to the heart of our evolving concept of the mind-body science. Dr. Mayo’s astute quote was from 1898 and underscores that for over 100 years physicians have suspected a strong link between the brain and the body. The quote reads: "Worry affects the circulation, the heart, the glands, the whole nervous system. I have never known a man who died of overwork, but many who died from doubt." We clearly see that Dr. Mayo was an early adopter of how profoundly disturbances of the mind could impact bodily functions in the periphery. This is particularly salient given that Western medicine has spent years artificially disconnecting psychiatry and the brain from general medicine and the body.
This concept was explored in my presentation from the 2009 U.S. Psychiatric and Mental Health Congress (USPC). Carney and colleagues1 showed that depression is an independent risk factor for death in a 5-year, follow-up study that examined survival in patients without depression versus patients with depression post-myocardial infarction. The results are impressive and show that the presence of either major or minor depression increases one’s risk for all-cause mortality.
0 Comment(s) Continue reading...
vmPFC Activity in MDD
February 10, 2010
Question:
"Is the increased activity in vmPFC in major depressive disorder (MDD) a function of loss of volume, as an adaptive mechanism, or is it a separate mechanism?"
Vladimir Maletic, MD :
The challenge in answering this question starts with the definition of vmPFC. Some authors define vmPFC (ventromedial prefrontal cortex) as a structure inclusive of BA (Brodmann Area) 11, 25, and 32; others limit it only to 11 and 32. Distinction is relevant because BA 25 is commonly considered to be the subgenual anterior cingulate cortex (sgACC). Although both of these areas have rich bidirectional connections with limbic areas, especially the amygdala, there are also notable functional differences.
0 Comment(s) Continue reading...
Adjunctive Anti-inflammatory Treatment and Depression
February 3, 2010
Question:
"Would use of adjunctive anti-inflammatories be useful for depression?"
Charles Raison, MD:
The short answer to this question is maybe. I know of two randomized, placebo-controlled studies showing that the addition of the COX-2 inhibitor celecoxib significantly increased response to a noradrenergic and to a serotonergic antidepressant.1,2 I also know of open data suggesting that the addition of 380 mg/day of aspirin to SSRIs converts nonresponders to responders.3,4 Several studies suggest that cortisone may improve depressive symptoms and be of benefit for conditions highly comorbid with depression, such as chronic fatigue syndrome,5,6 and in patients with autoimmune disorders, several studies confirm that tumor necrosis factor (TNF)-alpha antagonists, such as infliximab or etanercept, have antidepressant properties.7,8
10 Comment(s) Continue reading...
Cardiovascular Disease and Depression
January 27, 2010
Question:
"Could you please comment further on the relationship between depression and cardiovascular disease?"
Jon W. Draud, MD, MS:
This is an excellent question that underscores the mind-body connection we sought to explore at the 2009 U.S. Psychiatric and Mental Health Congress (USPC) in Las Vegas. The connection between depression and cardiovascular illness is quite robust and there is a wealth of literature to support it. Essentially, due to a hyperactive hypothalamic-pituitary-adrenal axis we believe that there are alterations in the periphery of cytokine levels, cortisol levels, and catecholaminergic tone. This primes the heart and other organ systems for numerous diseases.
I would like to examine several of the studies referenced at USPC to illustrate the point further. First, Whang and colleagues1 looked at over 63,000 patients and illustrated a correlation between depression status and sudden cardiac death, fatal coronary disease, and non-fatal myocardial infarction (MI).
3 Comment(s) Continue reading...
Exercise and Depression
January 20, 2010
Question:
"As a mental health professional, what should I know about physical exercise when I am treating my patients with major depression?"
Rakesh Jain, MD, MPH:
Even though mental health professionals are known as‘mind’clinicians, over the last decade published studies have shownthat we are the quintessential mind-body clinician. Emerging data on the use of physical exercise to treat depression powerfully reinforces this very message—that depression is a mind-body disease and treating it requires a mind-body approach.
We have long advocated physical exercise for our patients, but primarily for its clear and convincing positive benefits on physical health. You may be surprised to hear that the data on exercise’s effects on mental health are very significant too! In fact, the data is so impressive that I am beginning to recommend it to every patient with a mood disorder that I treat.
19 Comment(s) Continue reading...