Research breakthrough in understanding treatment resistant depression

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A pioneering research study using brain imaging has yielded new clues to help sufferers from severe depression who do not respond to conventional treatment

Around 5 million people in the UK experience depression at any one time. Whilst a number of successful treatments, both pharmacological and psychotherapeutic, are available and many people make a full recovery about 30 – 40% of people are resistant to conventional therapies. For them their depression is an enduring, debilitating disease and for some, the only treatment options left include psychosurgery and ECT.

Now an international team of researchers have discovered that brain activity differs significantly between healthy individuals and those suffering from treatment-resistant clinical depression.

Announcing their results in Biological Psychiatry, (October 15, 2003) the researchers were led by consultant psychiatrist, Professor Tonmoy Sharma, Director of the Clinical Neuroscience Research Centre in Dartford. He says: “This is a significant step in unravelling the reasons why these people may not be responding to the antidepressant drugs currently available.”

The study, the most significant to date to have investigated dysfunction in different parts of the brain in treatment-resistant depression, also heralds a new era in drug development. There are already benchmark drugs for treatment-resistant schizophrenia, but there is no equivalent treatment for treatment-resistant depression at the moment. This development in the understanding of the biological basis of treatment-resistant depression gives hope to scientists searching for a much- needed “atypical” antidepressant.

Abnormalities in particular regions of the brain are linked to depression. However little is known about how the neural network within the brain reacts to emotional stimuli. Previous research investigating people with depression focused on the reaction to stimuli that induce a negative emotion or on the brain in a resting state. But now, for the first time, Professor Sharma’s group have studied the reaction to the negative and positive mood inducing stimuli.

Six women with treatment resistant depression were recruited to the study, alongside six healthy female volunteers. The participants viewed a series of images that contained a picture and a caption while the researchers observed their emotional reaction using a brain imaging technique, known as functional magnetic resonance imaging (fRMI). This procedure is invaluable in tracking brain activity, and can pinpoint areas of the brain used in specific tasks.

The team found that people with depression processed their emotional response to the images differently from the healthy individuals. Some parts of the brain were less active in people with depression than the control group, while other areas showed greater activity. For instance activities in some regions of the brain, such as the rostral anterior cingulate, were reduced in people with depression compared to the healthy participants. However the team noticed that an area of the brain, the subgenual cingulate, associated with sadness in healthy people, was activated by the positive images shown to the participants with depression.

Reference:

Neural Abnormalities during Cognitive Generation of Affect in Treatment Resistant Depression Veena Kumari, Martina T. Mitterschiffthaler, John D. Teasdale, Gin S. Malhi, Richard G Brown, Vincent Giampietro, Michael J. Brammer, Lucia Poon, Andrew Simmons, Steven CR Williams, Stuart A. Checkley, Tonmoy Sharma. (Biological Psychiatry 15 October 2003)

Another study by the same group which gives insight on the research is:

Neural response to pleasant stimuli in anhedonia: an fMRI study Martina T. Mitterschiffthaler, Veena Kumari, Gin S. Malhi, Richard G Brown, Vincent Giampietro, Michael J. Brammer, Lucia Poon, Andrew Simmons, John Suckling, Christopher Andrew and Tonmoy Sharma (NEUROREPORT 10 February 2003)

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