Treating depression with electroconvulsive therapy

Robin Wulffson MD's picture
depression, electroconvulsive therapy, ECT, brain, treatment
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Major depression affects 15 million adults in the U.S., and the World Health Organization (WHO) projects that by 2020, it will be the largest contributor to disability in the world after heart disease. Electroconvulsive therapy (ECT) has been used for more than 70 years to treat depression and other mental conditions. It involves subjecting the brain to an electric shock, which results in seizures.

The use and indications of ECT has been subject to significant controversy. Various theories have been proposed as to its mode of action; however, none have been proven. New studies; however, have provided clues regarding how and why ECT works and what is going on in the brain of depressed individuals. Researchers in the United Kingdom published a new study online on March 19 in the journal Proceedings of the National Academy of Sciences (PNAS). The researchers claim that they have discovered how and why ECT works. Another study, published online in the journal PLoS ONE by UCLA researchers on February 27. It examined the brain connections in depressed individuals.

Symptoms related to depression include anxiety, poor attention and concentration, memory issues, and sleep disturbances. The multitude of related symptoms suggested to UCLA researchers that depression may be related to a malfunction between brain networks linking different sections of the brain. In their February 27, they announced that they had determined that depressed individuals suffer from increased connections between brain areas—in a word, they are hyper-connected.

The researchers reported that their study was the largest of its kind to date; it evaluated the functional connections of the brain in 121 adults diagnosed with a major depressive disorder (MDD). They measured the synchronization of electrical signals from the brain (brain waves) in order to evaluate networks connecting different brain regions. "The brain must be able to regulate its connections to function properly," noted the study's first author, Dr. Andrew Leuchter, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. He added, "The brain must be able to first synchronize, and then later desynchronize, different areas in order to react, regulate mood, learn and solve problems." He explained that the depressed brain maintains its ability to form functional connections; however, it loses the ability to turn these connections off. He noted that the inability to control how different brain areas work together might explain the underlying mechanisms of depression.

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Some previous studies have suggested that abnormal patterns of connections might be present in MDD, the researchers employed a new method called "weighted network analysis" to examine overall brain connections. They found that the depressed individuals exhibited increased synchronization across all frequencies of electrical activity; they noted that this indicated dysfunction in many different brain networks. Dr. Leuchter explained that brain activity in some of these networks regulates the release of serotonin and other brain chemicals that help control mood. He noted, "The area of the brain that showed the greatest degree of abnormal connections was the prefrontal cortex, which is heavily involved in regulating mood and solving problems… When brain systems lose their flexibility in controlling connections, they may not be able to adapt to change.

He concluded, “[An] important question is, to what extent do abnormal rhythms drive the abnormal brain chemistry that we see in depression? We have known for some time that antidepressant medications alter the electrical rhythms of the brain at the same time that levels of brain chemicals like serotonin are changing. It is possible that a primary effect of antidepressant treatment is to 'repair' the brain's electrical connections and that normalizing brain connectivity is a key step in recovery from depression. That will be the next step in our research."

It appears that the UK researchers are on the same wavelength—pardon the pun—as the UCLA researchers. They have determined that ECT affects the way different parts of the brain involved in depression communicate with each other. They reported that ECT appears to turn down overactive connections between parts of the brain that control mood and parts that control thinking and concentrating. Their ECT study involved using functional magnetic resonance imaging (fMRI) to scan the brains of nine severely depressed patients before and after ECT; they then applied complex mathematical analyses to investigate brain connectivity. Brain hyper-connectivity was decreased after ECT treatment and the patients’ depression decreased.

UCLA researchers have also employed electrical stimulation to treat depression. On September 2, 2010, UCLA researchers released the results of a clinical trial on a unique new therapy that applies electrical stimulation to a major nerve emanating from the brain. The technique, trigeminal nerve stimulation (TNS) achieved an average of a 70% reduction in symptom severity of depression over an eight-week study period. The study's principal investigator, Dr. Ian A. Cook, the Miller Family Professor of Psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, noted that 80% of the subjects achieved remission. The stimulator that was used in the depression clinical trial is about the size of a large cell phone. Two wires from the stimulator are passed under the clothing and connected to electrodes attached to the forehead by adhesive. The electrodes transmit an electrical current to the nerve. All the patients in the trial used the device for approximately eight hours every night while asleep. In contrast to antidepressants, no major side effects were noted.

Dr. Cook stated, “The major branches of the trigeminal nerve in the face are located close to the surface of the skull and can be stimulated either with non-invasive external electrodes, as we used in this trial, or with minimally invasive subcutaneous electrodes.” He added that some patients may prefer to have miniature subcutaneous electrodes implanted under the skin rather than applying new electrodes daily.

References:
Proceedings of the National Academy of Sciences
Plos One

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