# "Depression Switch" - more understanding of brain,



## Dreamer (Aug 9, 2004)

*I was afraid this would get lost in the "Other Mental Illnesses" Forum. Sorry I posted here. A fascinating, very lengthy, article on treatment resistant depression and the use of Deep Brain Stimulation which provided immediate relief for one woman.

It is seven pages long, so I've given some highlights ...*

http://www.nytimes.com/2006/04/02/m...e1ffa4ebbdf66b0d&ex=1144209600&pagewanted=all

*The New York Times
April 2, 2006
A Depression Switch? 
By DAVID DOBBS*

*Deanna Cole-Benjamin never figured to be a test case for a 
radical new brain surgery for depression. Her youth contained no 
traumas; her adult life, as she describes it, was blessed. At 22 
she joined Gary Benjamin, a career financial officer in the 
Canadian Army, in a marriage that brought her happiness and, in the 
1990's, three children. They lived in a comfortable house in 
Kingston, a pleasant university town on Lake Ontario's north shore, 
and Deanna, a public-health nurse, loved her work. But in the last 
months of 2000, apropos of nothing ? no life changes, no losses ? 
she slid into a depression of extraordinary depth and duration.

"It began with a feeling of not really feeling as connected to 
things as usual," she told me one evening at the family's 
dining-room table. "Then it was like this wall fell around me. I 
felt sadder and sadder and then just numb."*

Her doctor prescribed progressively stronger antidepressants, but 
they scarcely touched her. A couple of weeks before Christmas, she 
stopped going to work. The simplest acts ? deciding what to wear, 
making breakfast ? required immense will. Then one day, alone in 
the house after Gary had taken the kids to school and gone to work, 
she felt so desperate to escape her pain that she drove to her 
doctor's office and told him she didn't think she could go on 
anymore.

*EDIT.......................*

They drove to the Providence Continuing Care Center's mental-health 
hospital, still known locally as the Kingston Psychiatric Hospital, 
or K.P.H., its name when it was built in the 1950's. "It's a dingy, 
archaic place," Deanna said, "typical of older mental hospitals." 
There, in the locked ward that also contained psychotic patients, 
she would spend the next 10 months straight and about 85 percent of 
the three years after that. Her depression would prove resistant to 
every class of antidepressant, numerous combinations of 
antidepressants and anti-anxiety drugs, intensive psychotherapy and 
about a hundred sessions of electroconvulsive therapy. Patients who 
have failed that many treatments usually don't emerge from their 
depressions.

*Finally, in the spring of 2004, Deanna's psychiatrist at the 
hospital, Dr. Gebrehiwot Abraham, received a fax from a University 
of Toronto research team asking if he had an appropriate candidate 
for a clinical trial of a new, experimental surgery for 
treatment-resistant depression. The operation borrowed a procedure 
called deep brain stimulation, or D.B.S., which is used to treat 
Parkinson's. It involves planting electrodes in a region near the 
center of the brain called Area 25 and sending in a steady stream 
of low voltage from a pacemaker in the chest. One of the study's 
leaders, Dr. Helen Mayberg, a neurologist, had detected in 
depressed patients what she suspected was a crucial dysfunction in 
Area 25's activity. She hypothesized that the electrodes might 
modulate the area and ease the depression.*

The procedure, Dr. Abraham told Deanna and Gary, had worked safely 
in thousands of Parkinson's patients. But it would carry some risk 
of neural complications (it was, after all, brain surgery), it 
would be uncomfortable and it might not work.

"We were in tears," said Deanna, who is now 41. "We felt we'd tried 
everything and nothing worked. But we talked about it and decided,

'Well, what have we got to lose?"'

*What she hoped to lose, of course, was her depression. But 
depression, which 5 to 10 percent of Americans suffer in any given 
year and about 15 percent will suffer in their lifetimes, can be 
hard to lose. Drugs, as shown in a comprehensive study released 
last month by the National Institute of Mental Health, are 
effective in only half of patients with major depression.

Psychotherapy does no better. For those people who are not helped 
by therapy or drugs, electroconvulsive therapy, or ECT, can bring 
relief. But few of those cures are complete. These therapies 
usually ease rather than cure depression while sometimes bringing 
side effects like insomnia or memory loss, and their potency often 
proves fleeting; as many as half to two-thirds of those 
successfully treated relapse within two years.

Neither 
neuroscientists nor psychiatrists can say exactly what depression 
is. Neurologically and psychologically, what Hippocrates called the 
"black bile" and Susan Sontag "melancholy minus its charms" 
presents an almost impossibly complicated puzzle.*

*EDIT..............*

As it turned out, *8 of the 12 patients he operated on, including 
Deanna, felt their depressions lift while suffering minimal side 
effects ? an incredible rate of effectiveness in patients so 
immovably depressed. Nor did they just vaguely recover. Their 
scores on the Hamilton depression scale, a standard used to measure 
the severity of depression, fell from the soul-deadening high 20's 
to the single digits ? essentially normal. They've re-engaged their 
families, resumed jobs and friendships, started businesses, taken 
up hobbies old and new, replanted dying gardens. They've regained 
the resilience that distinguishes the healthy from the 
depressed.*

These results brought a marvelous surprise to both the patients and 
the doctors involved ? and nervous anticipation about whether their 
luck will hold. Though a few of the patients are more than two 
years out from the surgery, none completely trust their cure. No 
one can tell them for sure that it will last, and they 
worry.................

*EDIT...............................*

Mayberg's focus on Area 25 tests the emerging "network" model of 
mood disorders, a new way of looking at psychiatric conditions that 
isn't restricted by the neurochemical model of mood that has 
dominated over the past quarter century or so. Rather, it 
incorporates neurochemistry into the concept of the brain as a 
circuit board or wiring diagram. The network model carries profound 
implications for research and, ultimately, treatment. *

The 
Prozac revolution showed everyone that tweaking neurochemistry can 
dampen and sometimes extinguish depression ? but only through a 
generalized approach, hitting the entire brain. ("Carpet-bombing," 
one neuroscientist calls it.) And the 50 percent success rate of 
antidepressant drugs suggests that they aren't hitting depression's 
central mechanism. The network approach, on the other hand, focuses 
on specific nodes, pathways and gateways that might be approached 
with various treatments ? electrical, surgical or pharmacological. 
This small trial appears to confirm this model so emphatically that 
it's already changing the neuropsychiatric view of the brain and 
the direction of research.*

*EDIT.....................................*

........this is the beginning of a new way of understanding 
depression."

*BIG EDIT: History of depression research by Mayberg.*

By the 1990's, Mayberg was trying to define the network that goes 
awry in depression. She and other researchers soon established that 
*depression involved abnormal patterns of activity in a network 
that includes limbic areas (a cluster of evolutionarily older brain 
areas around the top of the brain stem), which control basic 
emotions and drives like fear, lust and hunger, and the newer 
cortex and subcortex responsible for thought, memory, motivation 
and reward.*

*EDIT.............*

They found that Area 25 was smaller in most depressed patients; 
that it lighted up in every form of depression and also in 
nondepressed people who intentionally pondered sad things; that it 
dimmed when depression was successfully treated; and that it was 
heavily wired to brain areas modulating fear, learning, memory, 
sleep, libido, motivation, reward and other functions that went 
fritzy in the depressed. It seemed to be a sort of junction box, in 
short, whose malfunction might be "necessary and sufficient," as 
Mayberg put it, to turn the world dim. Maybe it could provide a 
switch that would brighten the dark.

*EDIT................................[Association w/work on 
Parkinsons]*

Depression is more elusive than Parkinson's. But approaching Area 
25 with D.B.S. allowed the researchers to use a known tool. 
Neurosurgeons found as early as the 1950's that they could treat 
Parkinson's by destroying a small portion of the hyperactive globus 
pallidus, a brain area that is crucial to movement. The treatment 
illustrated one of the brain's many oddities: some areas can cause 
more trouble when they are excessively active than when they have 
no activity at all.

*EDIT.......................................*

Mayberg knew all this from the literature and learned more in 
conversations with Lozano. She grew increasingly convinced that 
applying D.B.S. to Area 25 might control depression.

*EDIT...........................................*

*[Excellent description of endogenous depression - treatment 
resistant]

Occasionally, Deanna felt good enough to go home. This feeling 
seldom lasted more than a few days. "You could tell she was getting 
bad again when she couldn't sleep," Gary said. "That was the red 
flag. She'd be around the house all night, watching TV, up worried, 
cleaning. Then she'd get worse each day. Her eyes got that sunken 
look. Those were the scariest times, when she was getting like that 
and I would drop the kids at school and go to work and know she was 
home alone."

During the bad periods, which was much of the time, Deanna thought 
about suicide almost constantly. Through the windows of the locked 
ward she could see Lake Ontario, cold and immense. While she was 
there, one patient managed to reach the lake, beyond the parking 
lot and a grove of trees, and drown himself. Deanna thought 
obsessively of doing the same.

"I imagined that all the time," she said. "That I would walk out 
there and walk into the lake and that would be it."
As the months and years passed and all treatments failed, it began 
to feel as if there were only one way out.

"It started to seem like, this is not going to stop," Gary said. 
"This is our life now. There were times I thought that it was going 
to end" ? he

looked across the table at Deanna ? "only when you committed 
suicide."

"The worst part for me," Deanna said, "was not being able to feel 
anything for my children. To hug them, to have them hug me, and 
feel nothing. That was devastating. An awful, awful place to 
be."*

*EDIT........Description of surgery...........*

Gary found the frame more than he could take. He kissed his wife 
and went elsewhere, hoping she wouldn't be a vegetable when he next 
saw her. Then Deanna was rolled to an M.R.I. machine, where scans 
would be taken; the scans would help guide Lozano in placing the 
electrodes.

During the hour or so while the computer processed the scans, 
Deanna chatted with Mayberg. The day before, she told Mayberg, on 
video, that what she most wanted was to hold her children and feel 
it.

*EDIT...........Description of surgery..............*

...........Now Lozano threaded a guide tube ? "It's a straight 
shot," he said later, "really quite easy" ? down between crevices 
and seams to one side of Area 25, which is in two small lobes at 
the midline of the brain. He slid the first electrode and its lead 
down the tube, then repeated this for the other side. All this took 
nearly two hours. After he double-checked his locations, he wired 
the leads to a pacemaker and gave Mayberg a nod. They could turn it 
on anytime now.

Mayberg had squeezed into a spot at Deanna's side some time before. 
She had told Deanna that if anything felt different, she should say 
so. Mayberg wasn't going to tell her when the device was activated.

"Don't try to decide what's important," Mayberg told her. "If your 
nose itches, I want to know." Now and then the two would chat. But 
so far Deanna hadn't said much.

*"So we turn it on," Mayberg told me later, "and all of a 
sudden she says to me, 'It's very strange,' she says, 'I know 
you've been with me in the operating room this whole time. I know 
you care about me. But it's not that. I don't know what you just 
did. But I'm looking at you, and it's like I just feel suddenly 
more connected to you.' "

Mayberg, stunned, signaled with her hand to the others, out of 
Deanna's view, to turn the stimulator off.

"And they turn it off," Mayberg said, "and she goes: 'God, it's 
just so odd. You just went away again. I guess it wasn't really 
anything.'*

"It was subtle like a brick," Mayberg told me. "There's no reason 
for her to say that. Zero. And all through those tapes I have of 
her, every time she's in the clinic beforehand, she always talks 
about this disconnect, this closeness and sense of affiliation she 
misses, that was so agonizingly painful for her to lose. And there 
it was. It was back in an instant."

Deanna later described it in similar terms.* "It was literally 
like a switch being turned on that had been held down for years," 
she said. "All of a sudden they hit the spot, and I feel so calm 
and so peaceful. It was overwhelming to be able to process emotion 
on somebody's face. I'd been numb to that for so long."

It worked that way for other patients too. For those for whom it 
worked, the first surges of mood and sensation were peculiar to 
their natures. Patient 4, for instance, was fond of taking walks, 
and she had previously told Mayberg that she knew she was getting 
ill when whole landscapes turned dim, as if "half the pixels went 
dark." Her first comment when the stimulator went on was to ask 
what they'd done to the lights, for everything seemed much 
brighter. Patient 5, an elite bicycle racer before his depression, 
told me that a pulling that he had long felt in his legs and gut, 
"as if death were pulling me downward," had instantly ceased.

Patient 1, who in predepression days was an avid gardener, amazed 
the operating room by announcing that she suddenly felt as if she 
were walking through a field of wildflowers. Two days after going 
home, she put a scarf over her shaved, stitched head, found her 
tools and went out to reclaim her long-neglected gardens.*

Not all was light and flowers. On a purely biological level, the 
improvement made by D.B.S. sometimes amplified the side effects of 
the high doses of medication the patients had been taking. Doctors 
don't quite understand this phenomenon, but they see it happen in 
other instances too; it is as if the patient, deadened, is again 
made sensate. Deanna broke out in hives and felt nauseated; her 
hands shook. These symptoms eased when she (as several of the 
patients have done) reduced her meds ? slowly, so as not to 
introduce new variables. She now takes standard doses of Effexor, 
an antidepressant, and Seroquel, an anti-psychotic drug.

*EDIT.........................*

This transition is not back to a former self and family but to a 
new one. Gary Benjamin says he sees similar things in military 
families. "These soldiers get sent away for six months, they come 
back and all they want to do is return to their old home. But their 
old home isn't there, because everybody's changed. It takes some 
tough rearranging sometimes."

For a change so profound, these seem acceptable adjustments. And 
the treatment so far seems remarkably free of side effects. No one 
has suffered significant neural complications, probably because, 
unlike ECT, which sends 70 to 150 volts through the entire brain, 
these electrodes deliver only about 4 volts to an area about the 
size of a pea.

*EDIT...........................*

*Regardless of how it pans out in the clinic, Mayberg and 
Lozano's D.B.S. study is already changing how neuroscientists and 
psychiatrists think about depression. One possibility, for 
instance, is that refining the networks that go awry in depression 
may reveal neurological subtypes of depression that can be 
diagnosed and treated differently. For example, Mayberg has already 
found that patients who respond well to Prozac usually show a 
change in their brain scans only a week after they start medication 
? even though they don't feel a difference for 3 to 10 weeks (a 
long and sometimes dangerous wait).*

*EDIT.................................*

This focus on neurotransmitters is the "bowl of soup" approach that 
Mayberg speaks of, and it has formed the bulk of depression 
research for more than two decades. Defining the networks the 
neurotransmitters move within, however ? and in particular 
identifying Area 25 as a key gateway within the depression network 
? will let researchers bring their neurochemical knowledge to bear 
on specific targets.

"With this D.B.S. work," Meyer-Lindenberg says, "they have 
characterized in detail a system" ? or network ? "underlying a 
major disorder. It's not a simplistic thing where you're saying 
it's all about this one area and you inject a current and 
everything's fine. It's a very complicated system. But this D.B.S. 
work shows us that amid this complicated system there is a place of 
overlap, a common denominator" ? Area 25 ? "that's a very 
attractive treatment target." Here, Meyer-Lindenberg says, 
researchers can try to apply the knowledge they've gained about 
neurochemistry and genetics. The network theory presents a 
framework around which to apply these perspectives.

*EDIT......................*

Along with redirecting research, the quieting of Area 25 may also 
change our conception of depression from a condition in which 
something is lacking ? self-esteem, resilience, optimism, energy, 
serotonin, you name it ? to one in which an active agent makes a 
person sick.

*"Most people think of depression as a deficit state," Mayberg 
says. "You're low, you're negative. But in fact, talk to a 
depressed person, and you have this bizarre combination of numbness 
and what William James called 'an active anguish.' 'A sort of 
psychical neuralgia,' he said, 'wholly unknown to healthy life.' 
You're numb but you hurt. You can't think, but you are in pain. 
Now, how does your psyche hurt? What a weird choice of words. But 
it's not an arbitrary choice. It's there. These people are feeling 
a particular, indescribable kind of pain."*

*This anguish, Mayberg suggests, is the manifestation of a neural 
circuit run amok.*

*EDIT...............................*

When Deanna, Gary and I finally finished talking, they insisted on 
driving me to my hotel. Halfway through town, Gary pulled off the 
main road, drove up a long, sinuous driveway and parked in a lot 
facing a dark, rambling building.

"This is the hospital," Gary said. "You see where Deanna stayed."
In the winter dark, the secure ward, off to the left, was easily 
discerned. It was a low wing, the only one with a few lights still 
on inside. Outside, bright flood lamps illuminated an exercise yard 
ringed by 20-foot-tall cyclone fencing topped with razor wire.

"And there's the lake," Gary said, motioning behind us. Through 
trees I could make out its blackness.

We sat several minutes, but no one said much.

"Well," Gary said, putting the minivan in gear. "We'd better get 
home."

*David Dobbs writes on science, medicine and culture. His last 
article for the magazine was about autopsy.*

*Copyright 2006
The New York Times*


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## Dreamland (Jun 1, 2005)

Fascinating!!


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## LOSTONE (Jul 9, 2005)

I hope that someday soon those doctors will be able to create a state of euphoria by using electrodes somehow. It would be cool if we could always be high and never come down and never have any bad side effects  . I don't think that I ever will let anyone mess with my brain like that though, it is to scary to think about what could go wrong.


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