Research Explores Mechanisms of Reward Processing in Patients with Treatment Resistant Major Depression

Newswise — An estimated 26.2 percent of Americans ages 18 and older – about one in four adults – suffer from a diagnosable mental disorder every year, which equates to approximately 57.7 million adults. Severe psychiatric illness affects a much smaller number of people – about 6 percent, or 1 in 17. Worldwide, an estimated 340 million people suffer from an episode of major depression every year. While most patients with major depression find relief through a combination of psychotherapy and medication, about 20 percent of patients fail to respond.

Researchers at Massachusetts General Hospital/Harvard Medical School studied the role of the ventral striatum of the brain in processing rewards in people with severe treatment resistant major depression. The results of this study, Human Ventral Striatum Neurons Encode Reward Expectation, will be presented by Sameer Sheth, MD, PhD, 4:16 to 4:30 pm, Monday, May 3, 2010, during the 78th Annual Meeting of the American Association of Neurological Surgeons in Philadelphia. Co-authors are Matthew Mian, BSE, John Gale, PhD, Christian Camargo, BA, Shaun Patel, BA, Jason Gerrard, MD, PhD, Darin Dougherty, MD, and Emad Eskandar, MD.

Dysfunction of circuits involving the ventral striatum can lead to a variety of disorders, including depression and OCD. Severely affected patients who do not respond to medical therapy may be candidates for surgical treatment, such as deep brain stimulation (DBS). DBS surgery involves the placement of tiny implantable electrodes into specific parts of the brain that are functioning abnormally. These electrodes emit tiny pulses of electrical stimulation to block the abnormal activity in the brain, which causes a variety of symptoms – such as pain, tremors, movement problems; as well as obsessions, moods and anxieties associated with psychiatric disorders. The success of DBS is dependent on the surgical team’s ability to precisely pinpoint the specific brain area for stimulation. The advantage of DBS is that it is reversible, nondestructive, and can be modified by adjustment of the stimulator settings after implantation.

“The ventral striatum plays an important role in the circuitry of reward-oriented behavior. This structure has extensive interconnections with both the limbic lobe of the brain, which processes emotions such as pleasure and fear, and the basal ganglia, which is involved in learning and motor control,” remarked Dr. Sheth.

The role of the human ventral striatum in reward processing was investigated in six patients with severe depression undergoing DBS in a Phase III clinical trial. Patient demographics: 5 male, 1 female; age range, 27-64.

The targeting electrode was placed in the ventral striatum and the patient was asked to play a computerized card game. In this simplified game of “War”, the patient won the hand if his or her card was higher than that of the computer. After seeing the card, the patient was allowed to place a bet of $5 or $20. The computer’s card was then revealed, followed by that hand’s payout/loss. To add an element of surprise, in 20 percent of hands, the bet was actually $50, unbeknownst to the player until payout.

“We discovered that the neurons changed their firing at various parts of the task. Some were particularly attuned to the expectation of upcoming reward arising from a strong hand, before the computer’s card was revealed. Others were more specifically activated after revealing the computer’s card, when the winner and loser of the hand were established. Interestingly, the expectation to win or lose the hand was generally associated with more activity than the expectation to draw. An unexpectedly large win or loss elicited the greatest and least activity, respectively,” stated Dr. Sheth.

“This research demonstrated that neurons in this region of the brain are sensitive to the expectation of upcoming reward. Understanding how the brain processes expectations for pleasurable results, modifies behavior to achieve those results, and reacts when those results are obtained or denied, will provide insight into normal reward-oriented behavior as well as conditions characterized by dysfunction of pleasure-related circuitry, including depression and addiction. A better appreciation of the mechanisms of reward processing in this region of the brain will hopefully improve our ability to treat disorders such as major depression,” concluded Dr. Sheth.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,600 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.

Disclosure: the author reports no conflicts of interest.