Posts Tagged ‘Major depressive disorder’

Larry H Bernstein, MD, …   received

http://No dishonour in depression/2013/06/23

Nature | Editorial

No dishonour in depression

The stigma associated with mental illness discourages investment in finding cures — even though the burden of the disorders on society is immense.

Comedian and writer Ruby Wax, a regular on British television, has clinical depression. In her book published last week, Sane New World (Hodder & Stoughton, 2013), she describes her struggles with different therapies and her fear of being ‘found out’. She is not alone. A 2010 survey in Europe revealed that 38% of people had a diagnosed mental disorder — including 7% with major depression. The proportion is likely to be similar in all populations, even in Africa, where psychiatric disease barely features on the health agenda.

The stigma attached to such disorders means that many people do not admit to their illness. The same stigma discourages investment, so that research funding is not proportional to the distress these disorders cause. Why lobby for better treatments for depression or schizophrenia when there are ‘real’ diseases out there, such as cancer?

Wax has been through the catalogue of available therapies and says that she has settled on an approach known as ‘mindfulness’, which helps to keep her depression under control. It may seem that the various therapies are inadequate, given that initial treatment of depression fails in 60% or more of cases. It is true that more treatment options are badly needed. Yet evidence-based cognitive behavioural therapies and drugs already developed by the pharmaceutical industry can work splendidly for long periods — if they are given to the right patients.

How do you recognize the right patients? Treatment decisions tend to be based on the preferences of physicians or their patients, often with a missionary zeal that gives no credence to the idea that a personalized approach would be more appropriate. Some hold that drugs have unacceptable side effects, whereas others say that cognitive therapy wastes time if the depressed brain is not first chemically lifted. It is becoming increasingly common to offer patients both treatments at once in the belief that drugs can prepare the brain to respond to cognitive therapy. That may be so, but it is also possible that the improved response rates are simply the result of catching two different populations.

The situation would improve drastically if simple tests could be developed to predict treatment outcome. Many exploratory clinical trials are now under way to search for biomarkers in genes or in the brain itself that might be predictive. This week sees the description of the first potential biomarker for discriminating between responders and non-responders to drugs or cognitive therapy in major depressive disorder (C. L. McGrath et al. JAMA Psychiatry http://dx.doi.org/10.1001/jamapsychiatry.2013.143; 2013).

“The stigma attached to mental disorders will fade when treatment becomes more effective.”

The study, led by neurologist Helen Mayberg of Emory University in Atlanta, Georgia, used positron emission tomography (PET) scans to measure metabolic activity in various brain regions of people with untreated depression (see also Nature http://doi.org/mtc; 2013). Patients were randomized into groups and treated for 12 weeks with either a commonly used antidepressant drug or cognitive behaviour therapy. The study’s results were clear-cut. Below-average activity in a brain area called the right anterior insula — which is linked with depression-relevant behaviours such as emotional self-awareness and decision-making — was associated with the patient showing a good response to cognitive behavioural therapy and a poor response to the drug. Above-average insula activity was predictive of the opposite.

This potential biomarker must still be tested in prospective clinical trials, which will assign patients to a treatment on the basis of their insula activity. It may fail. But if the biomarker comes up trumps, it could be transformative for many patients who would not have to endure two or three months of treatment trial and error.

If attitudes to mental illness do not change, even a successful biomarker of this type will have a hard time being accepted by health systems that foot the bills. Unlike a simple blood test, a PET scan is inconvenient because not all physicians have easy access to the technology and, at up to US$2,000 a shot, the procedure is not cheap. Although expensive treatments for other diseases and arguments about how to fund them are nothing new, this rational debate is harder for mental illnesses because of the irrational stigma that is attached to them.

Fifty years ago, the stigma surrounding cancer meant that physicians would sometimes lie to patients about the diagnosis from kindness. That has now faded because cancer is not always the death sentence it once was — thanks in part to the development of biomarkers that guide therapy. The stigma attached to mental disorders will also fade when treatment becomes more effective. But to break out of a vicious circle of underinvestment in a stigmatized disease area will require continued effort to get the problem recognized. This is a good week for that.

Journal name:
Date published:
(13 June 2013)


PET at NIH Clinical Center. General Electric (...

PET at NIH Clinical Center. General Electric (GE) Advance positron emission tomography (PET) scanner. (Photo credit: Wikipedia)

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Reporter: Aviva Lev-Ari, PhD, RN


Five Psych Disorders Have Common Genetics

By Michael Smith, North American Correspondent, MedPage Today

Published: February 27, 2013

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

share common genetic underpinnings — despite differences in symptoms and course of disease, researchers discovered.

In particular, single nucleotide polymorphisms (SNPs) in two genes involved in calcium-channel activity appear to play a role in all five, Jordan Smoller, MD, ScD, of Massachusetts General Hospital in Boston, and colleagues reported online in The Lancet.

The findings come from a genome-wide analysis of 33,332 cases and 27,888 controls in what the authors described as the largest-ever genetic study of psychiatric illness.

The results are “new evidence that may inform a move beyond descriptive syndromes in psychiatry and towards classification based on underlying causes,” Smoller said in a statement.

The findings are especially important because of revisions to the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, which have “reinvigorated debate about the validity of diagnostic boundaries,” the authors noted.

Indeed, the findings confirm previous evidence of “abundant pleiotropy in human complex disorders” – meaning the same genetic variant plays a role in several diseases, argued Alessandro Serretti, MD, PhD, and Chiara Fabbri of the University of Bologna in Italy.

For instance, they noted in an accompanying commentary, calcium signaling, a key regulator of the growth and development of neurons, was expected to be highly pleiotropic, an expectation that “has now been confirmed.”

But while some gene variants play a role in many disorders, there are almost certainly others that contribute to the “consistent diversity among disorders,” Serretti and Fabbri argued.

“Many genes and polymorphisms are expected to confer a liability to individual psychiatric diseases,” they wrote.

Nonetheless, they concluded, one implication of the study is that genetics “can contribute to prediction and prevention of psychiatric diseases, along with the identification of molecular targets for new generations of psychotropic drugs.”

But that is not likely to happen soon, according to Randy Ross, MD, of the University of Colorado School of Medicine in Aurora, Colo.

The study is a “beginning step to give us ideas that will eventually lead to new treatments,” he told MedPage Today.

In the long run, however, this study and subsequent research will change both diagnosis and treatment, Ross said, as psychiatric diseases are put on a biological footing.

The researchers found that SNPs (single-letter changes in the genetic code) in four regions were associated with all five disorders:

The statistical significance of all four surpassed the cutoff for genome-wide significance of P<5×10-8, Smoller and colleagues reported.

The calcium-channel gene CACNA1C  has been previously linked to

  • bipolar disorder,
  • schizophrenia, and
  • major depressive disorder, they wrote, as well as to
  • Timothy syndrome, a developmental disorder that can include autism.

The other calcium-channel gene has been linked to bipolar disorder in people of Han Chinese ethnicity, they added.

“Our results suggest that voltage-gated calcium signaling, and, more broadly, calcium-channel activity, could be an important biological process in psychiatric disorders,” they argued.

The region on chromosome 3 includes more than 30 genes, Smoller and colleagues noted, but previous research has linked SNPs in the area to

  • bipolar disorder,
  • schizophrenia, and
  • depression.

They cautioned that they compared models of cross-disorder effects with widely used goodness-of-fit measures, but different criteria might yield other results.

They also noted that diagnostic misclassification in the study cohort might produce “spurious evidence of genetic overlap between disorders,” although such errors would have to be widespread to affect the results.

Another limitation: the members of the study cohort were of European ancestry, so it’s not known if the findings apply to other populations.

The study was supported by the National Institute of Mental Health, as well as grants from the NIH, government grants from other countries, and private and foundation support.

The authors declared they had no conflicts.

The comment authors declared they had no conflicts.

Primary source: Lancet

Source reference:
Smoller JW, et al “Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis” Lancet 2013; DOI: 10.1016/S0140-6736(12)62129-1.

Additional source: Lancet
Source reference:
Alessandro Serretti, Chiara Fabbri “Shared genetics among major psychiatric disorders” Lancet 2013; DOI: 10.1016/S0140-6736(13)60223-8.


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Reporter: Aviva Lev-Ari, PhD, RN

Dysthymia: Often Chronic, Always Serious

Johns Hopkins Health Alert

Dysthymia is a chronic form of depression that is characterized by the presence of a depressed mood for most of the day, for more days than not, over a period of at least two years. Dysthymia may be intermittent and interspersed with periods of feeling normal, but these periods of improvement last for no more than two months.

Dysthymia often goes unnoticed. And because of its chronic nature, the person may come to believe, “I’ve always been this way.” In addition to depressed mood, symptoms of dysthymia include two or more of the following:

It is far better to treat dysthymia than to think of it as a minor condition. Bypassing treatment places people at increased risk for subsequently developing major depression. In fact, about 10 percent of people with dysthymia also have recurrent episodes of major depression, a condition known as double depression.

What causes of dysthymia?  Some medical conditions, including neurological disorders (such as multiple sclerosis and stroke), hypothyroidism, fibromyalgia and chronic fatigue syndrome, are associated with dysthymia. Investigators believe that, in these cases, developing dysthymia is not a psychological reaction to being ill but rather is a biological effect of these disorders.

There are many reasons for this connection. It may be that these medical conditions interfere with the action of neurotransmitters, or that medications (such as corticosteroids or beta-blockers) taken for a medical illness may trigger the dysthymia or that both dysthymia and the medical illness are related in some other way, reinforcing each other in a complicated manner.

Dysthymia can also follow severe psychological stress, such as losing a spouse or caring for a chronically ill loved one. Older people who have never had psychiatric disorders are particularly susceptible to developing dysthymia after significant life stresses.

Posted in Depression and Anxiety on October 16, 2012

Medical Disclaimer: This information is not intended to substitute for the advice of a physician. Click here for additional information: Johns Hopkins Health Alerts Disclaimer


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Reported by: Dr. Venkat S. Karra, Ph.D.


Brain structures involved in dealing with fear...


Major depression or chronic stress can cause the loss of brain volume, a condition that contributes to both emotional and cognitive impairment. Now a team of researchers led by Yale University scientists has discovered one reason why this occurs—a single genetic switch that triggers loss of brain connections in humans and depression in animal models.


The findings, reported in Nature Medicine, show that the genetic switch known as a transcription factor represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells, which in turn could contribute to loss of brain mass in the prefrontal cortex.


“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacology. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”


The research team analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation. The brains of patients who had been depressed exhibited lower levels of expression in genes that are required for the function and structure of brain synapses. Lead author and postdoctoral researcher H.J. Kang discovered that at least five of these genes could be regulated by a single transcription factor called GATA1. When the transcription factor was activated, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but also in symptoms of depression.


Duman theorizes that genetic variations in GATA1 may one day help identify people at high risk for major depression or sensitivity to stress.


“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” Duman said.










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