Key Brain Reward Region Not Activated By Positive Emotional Stimuli in Depression

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Brain imaging researchers at Weill Cornell Medical College in New York City have demonstrated dysfunction in a key brain region in major depression. Major depression, a mood disorder affecting millions of people, causes tremendous suffering with a large impact on public health. Brain imaging has recently produced significant advances concerning brain circuitry in major depression, mostly focusing upon negative emotion and mood regulation. In contrast, researchers at Weill Cornell have focused on the inability of many patients with depression to experience positive emotions.

In a study published in this month's issue of the American Journal of Psychiatry, the research team reports that patients with major depression, compared with healthy control subjects, fail to activate a critical deep brain area to positive emotional stimuli. The area is the ventral striatum, in the region of the nucleus accumbens, which has been associated with reward, motivation and salience. Furthermore, among patients, those who had more of a failure to activate this region under these conditions reported more lack of interest and pleasure in work or activities -- on "anhedonia" items of standardized clinical rating scales.

Recent models of depression have included the ventral striatum and motivational functions, among a number of regions and processes, but there has not previously been direct and specific evidence for positive emotion-related dysfunction in the region of the nucleus accumbens, with clinical correlation as well.

The current work addresses this issue with specifically-designed functional magnetic resonance imaging (fMRI) approaches. Study subjects silently read positive, neutral and negative emotional words on a screen as their pattern of brain activity was being measured. Targeted analyses allowed the scientists to test a hypothesis about the link between ventral striatal function, positive emotion and anhedonia, by comparing localized brain activity in the different experimental conditions, and determining its relationship to patients' depressive symptoms.

The research team in Weill Cornell's Department of Psychiatry was led by Drs. David Silbersweig and Emily Stern (senior authors, directors of the Functional Neuroimaging Laboratory, http://www.functionalneuroimaginglab.org/), and included Dr. Jane Epstein (first author), and Dr. James Kocsis (a clinical researcher of mood disorders and their treatment) and Dr. Hong Pan (image analysis scientist).

While follow-up studies will need to be performed, these initial findings help to clarify a biological underpinning for a central feature or sub-type of depression, and provide important information for the refinement of brain circuit models of depression.

The work also helps to provide a foundation for the development of improved treatment strategies, which are increasingly based upon specific brain targets and mechanisms. Such studies contribute to a growing body of neuroscientifiic work, leading to a greater understanding that conditions like depression have a biological foundation (are not just "psychological"). This understanding can help to de-stigmatize mental illness, so that people who are suffering receive greater support and get the help they need.


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