Friday, May 31, 2013

Blogging with an iPad App

I'm still struggling to master blogging with my iPad.

I stayed up to midnight last night here in Anchorage, and the sky still had some light! My childhood friend David flew up to town to celebrate his sister Melissa's 50th birthday, and we had a moose taco and Margarita diner on the sunny deck of Melissa's house. This should be a fun weekend as the part is tomorrow and I will reconnect with a lot of Alaskan friends.

My childhood friend David enjoys his Margarita in the bright Achorage sun at about 9 PM

Thursday, May 30, 2013

Bucky Quote

My pal David reminded me that Bucky Fuller came to East High School in Anchorage when we were going there. I'd forgotten that.

Sunday, May 26, 2013

Mystery of why we itch revealed by scientists

Mystery of why we itch revealed by scientists

Moving Back to the House

Today, I move back to mom's house -- my cold has abated. We have successfully avoided propagating the virus.

I've been spending too much time on Facebook. Some collectors have started a page on there named "The Charlton Arrow," and I love looking at all the old Charltons -- often discounted as shoddy, there's something that really appeals to me about certain issues -- gems among the dross.

Wednesday, May 22, 2013

Tomorrow's Task: Learn How to Import Images with the iPad

I must say, the importation of images to Blogger using my iPad is proving quite challenging, but I will find a way. Perhaps tomorrow I will dedicate myself to finding out how best to do it. Correcting typos in Blogger and Facebook is not all that easy, either. The cursor seems to warp around in the copy in strange places at strange times, resulting in misplaced corrections.

Speaking of Facebook, things don't seem quite as "intuitive," simple, or as consistent as they should be in accessing features. Be that as it may, as my friend Robin often says," Onward!"

Tuesday, May 21, 2013

Fresh Air

I'd forgotten how nice fresh air is. Anchorage is rated #15 on some list of the US cities with great air quality. I haven't looked up Dallas, but the air quality there is pretty rough on me, especially in the Summer. I have year-round allergies there and then add in the pollution and ozone, plus the artificial air-conditioning and it all makes for a less than appealing air brew.

Ahhh... breathe deep the pure air! Good snoozin' conditions.

Monday, May 20, 2013

More Anxiety, Please: Beware the Invasion of "Crazy Ants"

Mastering the iPad for Blogging

Now that I'm whiling away the hours in this hotel, perhaps I'll finally figure out how to add images to my blog with my iPad. Enthusiasts tout how much more intuitive Apple features are -- I find it ain't necessarily so. I'm sure I can do everything on the Apple devices that my PC could but I don't know how. It's much like learning a new language. Without images, I'm afraid my blog might get quite dull.

I also bought some Apple training (which I should be able to use in  Anchorage), so I should soon be much more skilled at using my new toys.

In the News: Better Math Through Electroshock?

Sunday, May 19, 2013

Don the Caregiver

I'm up in Alaska visiting my Mom. I came up here to help her with her heart monitoring and medical visits. However, on the plane I caught a cold and was summarily quarantined to a hotel for the next few days.  I went from  a would-be caregiver to "Typhoid Larry."

Oh well, staying away at the right time is also caregiving.

Monday, May 13, 2013

What is Atrial Fibrillation?

Atrial fibrillation is a type of heart disease that can lead to heart failure or stroke, and it is increasingly common. Educate yourself by learning about the causes and possible complications of atrial fibrillation

Since my own mother has this troublesome health condition, I thought I'd post this educational piece on Atrial Fibrillation, taken from today's health websites:

by Chris Iliades, medically reviewed by Pat F. Bass III, MD, MPH

Atrial fibrillation is a common form of heart disease and the most common cause of irregular heart rhythms that start in the upper chambers of the heart, called the atria. The term fibrillation refers to a fluttering, disorganized type of heartbeat — heart flutter.

"Atrial fibrillation tops the list of abnormalities that can occur in the heart's normal rhythm," says Douglas C. Westveer, MD, chief of cardiovascular disease at Beaumont Hospital in Troy, Mich.

According to the American Heart Association, about 2.2 million Americans have this form of heart disease. "Even more alarming, the incidence of atrial fibrillation is increasing and may reach epidemic proportions as more baby boomers enter older age groups," notes Dr. Westveer.

What Happens During Atrial Fibrillation?
A normal heart rhythm depends on a special sequence operating correctly. The two upper chambers of the heart are where a normal heartbeat begins. The electrical impulse for the beat starts in an area of the right atrium called the sinoatrial (SA) node. After the atria contract, the impulse goes to another node called the atrioventricular (AV) node. This node is located near the middle of the heart, and it triggers the lower chambers of the heart to contract, which pumps blood to the lungs and the body. When your heart is functioning normally, it beats about 60 to 100 times per minute.

But with atrial fibrillation, the SA node is not controlling the beginning of the hearbeat in the atria. "The atria are composed of millions of individual muscle cells that all contract together to create a normal heartbeat. During atrial fibrillation, each muscle cell contracts independently, resulting in the quivering action referred to as fibrillation," explains Westveer.

As the AV node gets overwhelmed with chaotic impulses from all over the atria, many impulses pass through, resulting in a rapid and irregular heartbeat that can get up to over 300 beats per minute.

Atrial Fibrillation Symptoms
There are two types of atrial fibrillation. "Some patients have 'paroxysmal' atrial fibrillation, a relapsing form of arrhythmia that often lasts for hours and may recur frequently over time. Others have a chronic type that continues for the remainder of their lives," says Westveer.

Symptoms of atrial fibrillation may include:

The sensation of heart flutter known as palpitations
Shortness of breath
Chest pain

Causes and Risk Factors for Atrial Fibrillation
Atrial fibrillation is associated with many different conditions including:

Heart disease
High blood pressure
Chronic lung disease
Overactive thyroid gland

A blood clot that lodges in the lungs In about 10 percent of people with atrial fibrillation, an underlying cause is never identified.

The biggest risk factors for atrial fibrillation are age and underlying heart disease, such as coronary artery disease or heart valve disease. Risk increases after age 60. By age 65, about 4 percent of people will have atrial fibrillation. Other risk factors include smoking, excessive caffeine, and stress.

Complications of Atrial Fibrillation
The two big complications from atrial fibrillation are blood clots and heart failure. Blood clots occur because blood that is not moving normally tends to clot. "Blood clots may form inside the atria over time and are a leading cause of stroke," says Westveer. A stroke can occur when a blood clot leaves the heart and gets lodged in an artery inside the brain. About 15 percent of all strokes happen in people with atrial fibrillation.

Heart failure occurs because the heart is not beating effectively and gradually gets weaker and weaker. Heart failure symptoms such as fatigue, shortness of breath, and fluid retention can develop over time as atrial fibrillation makes the heart work harder and grow weaker.

Fortunately there are many options to help prevent stroke and heart failure symptoms. "Although the prevalence of atrial fibrillation continues to increase, new treatment strategies are opening a brighter outlook for its management. The treatment choices should be fully discussed with your doctor," says Westveer.

Atrial fibrillation is more than just a heart flutter; it may be a sign of heart disease and it may put you at risk for stroke and heart failure. Talk to your doctor if you think you may have symptoms of atrial fibrillation.

Thursday, May 9, 2013

Neuronal Forest

I think that I shall never see
A poem lovely as a tree.
A tree whose hungry mouth is prest
Against the earth's sweet flowing breast;
A tree that looks at God all day,
And lifts her leafy arms to pray;
A tree that may in summer wear
A nest of robins in her hair;
Upon whose bosom snow has lain;
Who intimately lives with rain.
Poems are made by fools like me,
But only God can make a tree.

Joyce Kilmer

Brain Bugs: Graceful Degradation (Fault-Tolerance)

Neural web.

Graceful Degradation

Fault-tolerance or graceful degradation is the property that enables a system to continue operating properly in the event of the failure of (or one or more faults within) some of its components. If its operating quality decreases at all, the decrease is proportional to the severity of the failure, as compared to a naïvely-designed system in which even a small failure can cause total breakdown. Fault-tolerance is particularly sought-after in high-availability or life-critical systems.

From Dean Buonomano's website:

How does learning, memory, and behavior emerge from networks of neurons?

Learning and cognition are not a product of isolated neurons, but the emergent property of complex networks of neurons. While great progress continues to be made in molecular and cellular neuroscience, as well as in cognitive neuroscience, there is a gap between these levels of analyses. One of our main focuses is to bridge this gap and understand how does learning and other complex computations  emerge from the local circuits of the human brain.

How does the brain tell time?

While the brain's ability to tell time is a fundamental computation necessary for everything from speech recognition to anticipating events in the world around us, virtually nothing is known about how the brain tells time. We have hypothesized that timing is such an important component of brain function that most neural circuits are capable of telling time on the scale of milliseconds and seconds.

Answering the above questions is be necessary both to understand the brain and mind, and to unveil the causes of neurological disorders that impair learning, memory, and cognition.

NPR "Fresh Air" Audio Interview with Dean Buonomano about his book, "Brain Bugs."

Wednesday, May 8, 2013

On the Web: Bankers Behind Bars

Convicted Fraudsters:

Rajat Gupta: Ex-Goldman Rajat Gupta was sentenced to two years in prison for participating in one of the largest insider trading schemes in history.

Jerome Kerviel: Kerviel was found guilty of one of the world's most colosal trading frauds in 2010. He cost France's Société Générale bank 4.9 billion Euros. He was sentenced to 3 years in jail and was also sentenced to paying a $7 billion fine, The Guardian reports.

Steven Goldberg, Peter Grimm and Dominick Carollo: Goldberg, Grimm and Carollo were found guilty of conning the I.R.S. and cities in a "bid-rigging scheme" during their time at General Electric, Businessweek reports.

Raj Rajaratnam: Raj Rajaratnam, the former head of Galleon Management, was sentenced to 11 years in jail in October 2011, the longest prison term for insider trading to date, The Washington Post reports.

Bernie Madoff: In what is now considered to be one of the biggest and most famous Ponzi schemes in history, Madoff laundered about $65 billion, Forbes reports. Madoff defrauded thousands of investors, all of whom can be found on a 163-page list.

Nick Leeson: During Nick Lesson's time at Britain's Barings Bank, he lost 862 million pounds and even managed to level the 233-year-old bank itself, according to The Telegraph. He served four years in a Singapore jail before he was released early with life-threatening cancer.

Allen Stanford: Currently serving 110 years in prison, Allen Stanford was, at one time, one of the richest men in America, according to CNBC. He conned about 20,000 investors out of their money in a Ponzi scheme.

Garth Peterson: Garth Peterson, the former head of Morgan Stanley's Chinese real-estate investments unit, was sentenced to 9 months in jail last August for bribery, according to The Wall Street Journal.

Bradley Birkenfeld: Bradley Birkenfeld spent more than 2 years in jail for assisting in income tax evasion while working at UBS. He then volunteered inside information on Swiss banking to the I.R.S., and was rewarded with $104 million for being a whistle-blower, according to The New York Times.

Den Of Thieves: Dennis Levine, Martin Siegel, Ivan Boesky and Michael Milken defrauded Wall Street investors in the 1980's. In a scandalous series of events, Levine stole confidential documents from Lazard Freres investment bank, and the crew made use of inside information, according to The Daily Beast.

The Marvel Banner Lowered to Half-Mast: RIP Dan Adkins

The good doctor's first solo issue, Doctor Strange #169, June 1968. Dan Adkins cover art.

In 1964, during the period comic-book fans and historians call the Silver Age of Comics, Adkins joined the Wally Wood Studio as Wood's assistant. Wood and Adkins collaborated on a series of stories for Warren Publishing's black-and-white horror-comics magazines Creepy and Eerie. Adkins was among the original artists of Wood's T.H.U.N.D.E.R. Agents, for Tower Comics, drawing many Dynamo stories during his 16 months in the Wood Studio.[1]
His work as a penciler and inker appeared in 816 comic books, and he inked over 70 artists in the comics industry. He drew 132 covers for Marvel Comics, in addition to his many pages for Doctor Strange and other Marvel titles. Adkins has worked for a variety of comics publishers, including Charlton Comics, DC Comics (Aquaman, Batman), Dell Comics/Western Publishing, Eclipse Comics, Harvey Comics, Marvel, and Pacific Comics.[1]
In addition to penciling and inking, Adkins has also done cover paintings, including Amazing Stories, Eerie (issue 12) and Famous Monsters of Filmland (issues 42, 44). His magazine illustrations have been published in Argosy (with Wood), Amazing Stories, Fantastic, Galaxy Science Fiction, Infinity, Monster Parade, Science-Fiction Adventures, Spectrum, Worlds of If and other magazines.

Cellular Environment Controls Formation and Activity of Neuronal Connections

Neuron in the net: The illustration shows a neuron from the hippocampus of a mouse in cell culture, which is surrounded by a special structure of the extracellular matrix - a perineuronal net (blue). Various structures of the synapse are colored red, green and yellow. © RUB, LS Zellmorphologie und Molekulare Neurobiologie (Department of Cell Morphology and Molecular Neurobiology)

Neuroscience, May 6, 2013

Environment moulds behavior - and not just that of people in society, but also at the microscopic level. This is because, for their function, neurons are dependent on the cell environment, the so-termed extracellular matrix. Researchers at the Ruhr-Universität have found evidence that this complex network of molecules controls the formation and activity of the neuronal connections.

The team led by Dr. Maren Geißler and Prof. Andreas Faissner from the Department of Cell Morphology and Molecular Neurobiology reports in the Journal of Neuroscience in collaboration with the team of Dr. Ainhara Aguado, Prof. Christian Wetzel and Prof. Hanns Hatt from the Department of Cell Physiology.

In cooperation with Prof. Uwe Rauch from Lund University in Sweden, Bochum's biologists examined cells from the brains of two mouse species: a species with a normal extracellular matrix and a species which lacked four components of the extracellular matrix due to genetic manipulation, namely the molecules tenascin-C, tenascin-R, neurocan and brevican.

They took the cells from the hippocampus, a brain structure that is crucial for the long-term memory. The team not only examined neurons but also astrocytes, which are in close contact with the neurons, support their function and secrete molecules for the extracellular matrix.

Formation, stability and activity of the neuronal connections depend on the matrix

The researchers cultivated the neurons and astrocytes together for four weeks with a specially developed culture strategy. Among other things, they observed how many connections, known as synapses, the neurons formed with each other and how stable these were over time.

If either the astrocytes or the neurons in the culture dish derived from animals with a reduced extracellular matrix, these synapses proved to be less stable in the medium term, and their number was significantly reduced. Together with the Department of Cell Physiology at the RUB and the University of Regensburg, the team also showed that the neurons with a mutated matrix showed lower spontaneous activity than normal cells. The extracellular matrix thus regulates the formation, stability and activity of the neuronal connections.

The researchers also examined a special structure of the extracellular matrix, the so-called perineuronal nets, which the Nobel laureate Camillo Golgi first described more than a century ago.

They were significantly reduced in the environment of genetically modified cells.

More information: M. Geissler, C. Gottschling, A. Aguado, U. Rauch, C.H. Wetzel, H. Hatt, A. Faissner (2013): Primary hippocampal neurons, which lack four crucial extracellular matrix molecules, display abnormalities of synaptic structure and function and severe deficits in perineuronal net formation, Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.3275-12.2013

Journal reference: Journal of Neuroscience  

In the News: Effects of Stress On Brain Cells Offer Clues to New Anti-Depressant Drugs

Structure of protein SGK1.Based on PyMOL rendering of PDB 2R5T.

May 6, 2013 in Neuroscience

Research from King's College London reveals the detailed mechanism behind how stress hormones reduce the number of new brain cells - a process considered to be linked to depression. The researchers identified a key protein responsible for the long-term detrimental effect of stress on cells, and importantly, successfully used a drug compound to block this effect, offering a potential new avenue for drug discovery.

The study, published in Proceedings of the National Academy of Sciences (PNAS) was co-funded by the National Institute for Health Research Biomedical Research Centre (NIHR BRC) for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London.

Depression affects approximately 1 in 5 people in the UK at some point in their lives. The World Health Organisation estimate that by 2030, depression will be the leading cause of the global burden of disease. Treatment for depression involves either medication or talking therapy, or usually a combination of both.

Current antidepressant medication is successful in treating depression in about 50-65% of cases, highlighting the need for new, more effective treatments.

Depression and successful antidepressant treatment are associated with changes in a process called "neurogenesis"- the ability of the adult brain to continue to produce new brain cells. At a molecular level, stress is known to increase levels of cortisol (a stress hormone) which in turn acts on a receptor called the glucocorticoid receptor (GR). However, the exact mechanism explaining how the GR decreases neurogenesis in the brain has remained unclear.

Professor Carmine Pariante, from King's College London's Institute of Psychiatry and lead author of the paper, says: "With as much as half of all depressed patients failing to improve with currently available medications, developing new, more effective antidepressants is an important priority. In order to do this, we need to understand the abnormal mechanisms that we can target. Our study shows the importance of conducting research on cellular models, animal models and clinical samples, all under one roof in order to better facilitate the translation of laboratory findings to patient benefit."

In this study, the multidisciplinary team of researchers studied cellular and animal models before confirming their findings in human blood samples. First, the researchers studied human hippocampal stem cells, which are the source of new cells in the human brain. They gave the cells cortisol to measure the effect on neurogenesis and found that a protein called SGK1 was important in mediating the effects of stress hormones on neurogenesis and on the activity of the GR.

By measuring the effect of cortisol over time, they found that increased levels of SGK1 prolong the detrimental effects of stress hormones on neurogenesis. Specifically, SGK1 enhances and maintains the long-term effect of stress hormones, by keeping the GR active even after cortisol had been washed out of the cells.

Next, the researchers used a pharmacological compound (GSK650394) known to inhibit SGK1, and found they were able to block the detrimental effects of stress hormones and ultimately increase the number of new brain cells.

Finally, the research team were able to confirm these findings by studying levels of SGK1 in animal models and human blood samples of 25 drug-free depressed patients.

Dr. Christoph Anacker, from King's College London's Institute of Psychiatry and first author of the paper, says: "Because a reduction of neurogenesis is considered part of the process leading to depression, targeting the molecular pathways that regulate this process may be a promising therapeutic strategy. This novel mechanism may be particularly important for the effects of chronic stress on mood, and ultimately depressive symptoms. Pharmacological interventions aimed at reducing the levels of SGK1 in depressed patients may therefore be a potential strategy for future antidepressant treatments."

More information: Anacker, C. et al. 'A role for the kinase SGK1 in stress, depression and glucocorticoid effects on hippocampal neurogenesis' Proceedings of the National Academy of Sciences (PNAS) (May 2013)… s.1300886110

Wiki on SGK1:

Robert Dennis: Marvel Saga #3 Stat Replacement/Restoration

As purchased, with a photocopied title logo stat at the top. Art by Ron Frenz and John Byrne.

With carefully color-matched and re-sized title logo stat and additional caption boxes added.

Marvel Saga #3, February 1986 : "Book III: A Gathering of Dooms"

Wraparound cover by Ron Frenz and John Byrne. The Official History of the Marvel Universe continues as we witness the complete origin and history of Prince Namor and his first strike against the surface world. Plus, the conclusion to Spider-Man's origin, as well as the complete origin of Doctor Doom and his very first battle with the Fantastic Four. And, we meet the mysterious man known as Professor X. Featuring excerpts from Amazing Fantasy #15 (1962) , Fantastic Four #4 and #5 (1961), Fantastic Four Annual #1 and #2, Marvel Mystery Comics  #9 (1939), Sub-Mariner #1 and #8 (1968), Incredible Hulk #2 (1962) , Uncanny X-Men #38 (1963), and Giant Size Invaders #1 (1975).

Tuesday, May 7, 2013

John Alexander Interview

John Alexander preceded my years at SMU in the mid-seventies, but he was still very much a part of the Dallas art scene and showed at the old Delahunty Gallery in Dallas. He ran with artists James Surls, Dan Rizzie, Julian Schnabel, and some of the cast of Saturday Night Live. This interview on YouTube was nicely done.

John Alexander, Ship of Fools.

Artist John Alexander interviewed in his NYC painting studio. Features "Ship of Fools" from the exhibition "Creating the New Century: Contemporary Art from the Dicke Collection" at The Dayton Art Institute. Produced by B&B Arts: Ellie Bronson and Laurie Butler.

Monday, May 6, 2013

Priming and Semantic Networks

The extrastriate cortex (shown in orange and red) is believed to be involved in perceptual priming

From ye wiki:

Priming is an implicit memory effect in which exposure to a stimulus influences a response to a later stimulus. It can occur following perceptual, semantic, or conceptual stimulus repetition. For example, if a person reads a list of words including the word table, and is later asked to complete a word starting with tab, the probability that he or she will answer table is greater than if they are not primed.

Another example is if people see an incomplete sketch that they are unable to identify and they are shown more of the sketch until they recognize the picture, later they will identify the sketch at an earlier stage than was possible for them the first time.

The effects of priming can be very salient and long lasting, even more so than simple recognition memory. Unconscious priming effects can affect word choice on a word-stem completion test long after the words have been consciously forgotten.

Priming works best when the two stimuli are in the same modality. For example visual priming works best with visual cues and verbal priming works best with verbal cues. But priming also occurs between modalities, or between semantically related words such as "doctor" and "nurse".

In daily life

Priming is thought to play a large part in the systems of stereotyping. This is because attention to a response increases the frequency of that response, even if the attended response is undesired. The attention given to these response or behaviours primes them for later activation.

This can occur even if the subject is not conscious of the priming stimulus. An example of this was done by Bargh et al. in 1996. Subjects were implicitly primed with words related to the stereotype of elderly people (example: Florida, forgetful, wrinkle). While the words did not explicitly mention speed or slowness, those who were primed with these words walked more slowly upon exiting the testing booth than those who were primed with neutral stimuli.

Similar effects were found with rude and polite stimuli: those primed with rude words were more likely to interrupt an investigator than those primed with neutral words, and those primed with polite words were the least likely to interrupt. A Yale study showed that something as simple as holding a hot or cold beverage before an interview could result in pleasant or negative opinion of the interviewer.

These findings have been extended to therapeutic interventions. For example, Cox etal (2012) suggest that presented with a depressed patient who "self-stereotypes herself as incompetent, a therapist can find ways to prime her with specific situations in which she had been competent in the past... Making memories of her competence more salient should reduce her self-stereotype of incompetence."

The replicability and interpretation of goal-priming findings has become controversial. Recent studies have failed to replicate finds, including age priming, with additional reports of failure to replicate this and other findings such as social-distance also reported.


Many of the priming effects could not be replicated in further studies, casting doubt on their effectiveness or even existence. Nobel Laurate and psychologist Daniel Kahneman has called on social psychologists to check the robustness of priming studies in an open letter to the community, claiming that social psychology has become a "poster child for doubts about the integrity of psychological research." Other critics have asserted that priming studies suffer from major publication bias, experimenter effect and that criticism of the field is not dealt with constructively.


A technique called priming can demonstrate implicit memory. A person who sees the word yellow will be slightly faster to recognize the word banana as a word. This happens because the words yellow and banana are closely associated in memory.

What is "priming"? What is a "semantic network"?

Researchers sometimes envision a network of word meanings or semantic network somewhat like the diagram. The distance between words indicates the frequency with which the words are associated in everyday life. Because of these associations, activating one node of the network (showing the person one word) warms up or primes nearby words, speeding retrieval. This effect lasts about 30 minutes after exposure to the priming word.

Priming does not require conscious rehearsal of word meanings. The associations between words used in a priming experiment are not consciously memorized for purposes of the experiment; they are naturally occurring associations. (However, they are learned, and they can be culture-specific. Not every society has yellow school busses, for example.) No conscious strategy is required to show priming effects.

Brain-damaged and intoxicated people show the same priming effects as other people. This is another example of implicit memory. Indeed, the example used on the preceding page, about implicit vs. explicit memory, was also a form of priming. It involved degraded words, shown as a cue to recall words a person saw earlier in the experiment. In that case, the experimenters were interested in seeing whether the priming effect (showing the words earlier) would occur equally in drunk and sober subjects, which it did.

How does priming normally help language comprehension?

In normal reading, words seen ahead of the fixation point of the eye (in peripheral vision) are activated in semantic memory ("warmed up") so when the eye fixates upon them, their meanings are available faster. Similarly, in conversation, if you hear somebody say, "I ate a yellow" [followed by a muffled word that sounds like "an-an-an"] you might well hear "I ate a yellow banana" because you have a semantic network like the one in the diagram. The word banana is activated by its association to the word yellow, so you easily retrieve it even if the stimulus is partial or degraded. The memory retrieval is automatic, evoked by the situation, so this is an example of implicit memory.

On the Talk Nerdy to Me Blog: "Body Hacking"

Just how far could science boost athleticism? To a superhuman level.

Surgery, blood augmentation, and genetic modifications are all possible ways to enhance the human body and take our natural abilities to new heights. But how exactly would such "body hacking" work?

I had a chance to speak with Dr. Norman Fost, professor at University of Wisconsin School of Medicine, and Dr. Hugh Herr, who heads the biomechatronics research group at the MIT Media Lab -- both are experts on performance enhancement.

Saturday, May 4, 2013

Marvel Mania International Membership Card

Cool Jack Kirby Marvel character art, that he probably inked himself.

The Classic Thing by Jack Kirby and Joe Sinnott

Originally, sport trading cards were mostly head or body shots peppered with some action pictures, and some of Marvel's early offerings followed this standard format.

Others reprinted panels from the original comics. Products from this time period include the 1966 Marvel Super Heroes set from Donruss, like the one above.

As of 2010, the set of 66 cards was worth approximately $150, but the unopened packs can fetch $50 apiece. Occasionally, especially during the 1960s and 1970s, card sets would take a more humorous approach, such as 1976's Marvel Super Heroes Stickers, which booked at $90 for the 40 stickers and nine cards in the set.

Friday, May 3, 2013

Harry Callahan "Weed Against the Sky, Detroit"

Harry Callahan, Weed Against the Sky, Detroit, gelatin silver print, 1948/1970.

Harry Morey Callahan (1912-1999) was an influential twentieth century American photographer. Born in Detroit, Michigan, he worked in Chrysler when he was a young man then left the company to study engineering at Michigan State University. However he eventually dropped out, returned to Chrysler and joined its camera club. Callahan began teaching himself photography in 1938. He formed a friendship with Todd Webb who was also destined to become a photographer. A talk given by Ansel Adams in 1941 inspired him to take his work seriously. In 1941, Callahan and Webb visited Rocky Mountain State Park but didn't return with any photographs. In 1946 he was invited to teach photography at the Institute of Design in Chicago by László Moholy-Nagy. He moved to Rhode Island in 1961 to establish a photography program at the Rhode Island School of Design, teaching there until his retirement in 1977.

Dr. Frederic Wertham once observed in his infamous anti-comics book,  “there are pictures within pictures for those who know how to look.” Wertham illustrated in his 1954 expose, Seduction of the Innocent, examples of dirty pics one could find in children’s comic books. Here’s one the troubled Doctor found below, reprinted in Craig Yoe's book Weird But True 'Toon Factoids. What would FW make of the Harry Callahan photo above? Hey, now.

Thursday, May 2, 2013

In the News: US Suicide Rate Rose Sharply Among the Middle-Aged

by Mike Stobbe, AP Medical Writer

The suicide rate among middle-aged Americans climbed a startling 28 percent in a decade, a period that included the recession and the mortgage crisis, the government reported Thursday.

The trend was most pronounced among white men and women in that age group. Their suicide rate jumped 40 percent between 1999 and 2010.

But the rates in younger and older people did not change. And there was little change among middle-aged blacks, Hispanics and most other racial and ethnic groups.

Why did so many middle-aged whites take their own lives?

One theory suggests the recession caused more emotional trauma in whites, who tend not to have the same kind of church support and extended families that blacks and Hispanics do. Another theory notes that white baby boomers have always had higher rates of depression and suicide, and that has held true as they've hit middle age.

"Some of us think we're facing an upsurge as this generation moves into later life," said Dr. Eric Caine, a suicide researcher at the University of Rochester.

During the 1999-2010 period, suicide went from the eighth leading cause of death among middle-aged Americans to the fourth, behind cancer, heart disease and accidents.

The Centers for Disease Control and Prevention released the report, which was based on death certificates. People ages 35 to 64 account for about 57 percent of suicides.

During the period studied, the suicide rate for whites ages 35 to 64 spiked from about 16 suicides per 100,000 people to 22 per 100,000.

Suicide prevention efforts have tended to concentrate on teenagers and the elderly, but research over the past several years has begun to focus on the middle-aged. The new CDC report is being called the first to show how the trend is playing out nationally and to look in depth at the racial and geographic breakdown.

The suicide rate registered a statistically significant increase in 39 out of 50 states. The West had the highest suicide rate.

The report also unveiled surprising information about how middle-aged people kill themselves. Health officials have focused for years on drug overdoses, which are the most common manner of suicide attempt. But overdoses often don't result in deaths.

In the new report, hangings overtook drug overdoses among the middle-aged, becoming the second leading manner of death. But guns remained far in the lead and were the instrument of death in nearly half of all suicides in that age group in 2010.

The economy was in recession from December 2007 until June 2009. Even well afterward, polls showed most Americans remained worried about weak hiring, a depressed housing market and other problems.

From the Save a Friend Dept.: A Very Long Section of General Information About Suicide and Suicide Prevention

(Note: I have added this Suicide Prevention section to help save a life. Suicide prevention is everybody’s business. Educate our community that suicide is a preventable public health problem and should no longer be considered a taboo topic, and that through raising awareness and educating the public, we can save lives. )

Suicide is a significant cause of death in many Western countries, in some cases exceeding deaths by motor vehicle accidents annually. Many countries spend vast amounts of money on safer roads, but very little on suicide awareness and prevention, or on educating people about how to make good life choices.

Attempts at suicide, and suicidal thoughts or feelings are usually a symptom indicating that a person isn’t coping, often as a result of some event or series of events that they personally find overwhelmingly traumatic or distressing. In many cases, the events in question will pass, their impact can be mitigated, or their overwhelming nature will gradually fade if the person is able to make constructive choices about dealing with the crisis when it is at its worst.

Since this can be extremely difficult, this section is an attempt to raise awareness about suicide, so that we may be better able to recognize and help other people in crisis, and also to find how to seek help or
make better choices ourselves.


1. Why do people attempt suicide?

People usually attempt suicide to block unbearable emotional pain, which is caused by a wide variety of problems. It is often a cry for help. A person attempting suicide is often so distressed that they are unable to see that they have other options: we can help prevent a tragedy by endeavoring to understand how they feel and helping them to look for better choices that they could make. Suicidal people often feel terribly isolated; because of their distress, they may not think of anyone they can turn to, furthering this isolation.

In the vast majority of cases a suicide attemptor would choose differently if they were not in great distress and were able to evaluate their options objectively. Most suicidal people give warning signs in the hope that they will be rescued, because they are intent on stopping their emotional pain, not on dying.

2. Aren’t all suicidal people crazy?

No, having suicidal thoughts does not imply that you are crazy, or necessarily mentally ill. People who attempt suicide are often acutely distressed and the vast majority are depressed to some extent. This depression may be either a reactive depression which is an entirely normal reaction to difficult circumstances, or may be an endogenous depression which is the result of a diagnosable mental illness with other underlying causes. It may also be a combination of the two.

The question of mental illness is a difficult one because both these kinds of depression may have similar symptoms and effects. Furthermore, the exact definition of depression as a diagnosable mental illnesses (i.e. clinical depression) tends to be somewhat fluid and inexact, so whether a person who is distressed enough to attempt suicide would be diagnosed as suffering from clinical depression may vary in different peoples opinions, and may also vary between cultures.
It’s probably more helpful to distinguish between these two types of depression and treat each accordingly than to simply diagnose all such depression as being a form of mental illness, even though a person suffering from a reactive depression might match the diagnostic criteria typically used to diagnose clinical depression. For example, Appleby and Condonis[1] write:
The majority of individuals who commit suicide do not have a diagnosable mental illness. They are people just like you and I who at a particular time are feeling isolated, desperately unhappy and alone. Suicidal thoughts and actions may be the result of life’s stresses and losses that the individual feels they just can’t cope with.

In a society where there is much stigma and ignorance regarding mental illness,a person who feels suicidal may fear that other people will think they are “crazy” if they tell them how they feel, and so may be reluctant to reach out for help in a crisis. In any case, describing someone as “crazy”, which has strong negative connotations, probably isn’t helpful and is more likely to dissuade someone from seeking help which may be very beneficial, whether they have a diagnosable mental illness or not.

People who are suffering from a mental illness such as schizophrenia or clinical depression do have significantly higher suicide rates than average, although they are still in the minority of attemptors. For these people, having their illness correctly diagnosed can mean that an appropriatetreatment can begin to address it.

For more information about clinical depression, see the FAQ, available from:

3. Doesn’t talking about suicide encourage it?

It depends what aspect you talk about. Talking about the feelings surrounding suicide promotes understanding and can greatly reduce the immediate distress of a suicidal person. In particular, it is OK to ask someone if they are considering suicide, if you suspect that they are not coping. If they are feeling suicidal, it can come as a great relief to see that someone else has some insight into how they feel.
This can be a difficult question to ask, so here are some possible approaches:

“Are you feeling so bad that you’re considering suicide?”
“That sounds like an awful lot for one person to take; has it made you think about killing yourself to escape?”
“Has all that pain you’re going through made you think about hurting yourself?”
“Have you ever felt like just throwing it all away?”

The most appropriate way to raise the subject will differ according to the situation, and what the people involved feel comfortable with. It’s also important to take the persons overall response into consideration when interpreting their answer, since a person in distress may initially say “no”, even if they mean “yes”. A person who isn’t feeling suicidal will usually be able to give a comfortable “no” answer, and will often continue by talking about a specific reason they have for living. It can also be helpful to ask what they would do if they ever were in a situation where they were seriously considering killing themselves, in case they become suicidal at some point in the future, or they are suicidal but don’t initially feel comfortable about telling you.

Talking exclusively about how to commit suicide can give ideas to people who feel suicidal, but haven’t thought about how they’d do it yet. Media reports that concentrate solely on the method used and ignore the emotional backdrop behind it can tend to encourage copy-cat suicides.

4. So what sort of things can contribute to someone feeling suicidal?
People can usually deal with isolated stressful or traumatic events and experiences reasonably well, but when there is an accumulation of such events over an extended period, our normal coping strategies can be pushed to the limit.

The stress or trauma generated by a given event will vary from person to person depending on their background and how they deal with that particular stressor. Some people are personally more or less vulnerable to particular stressful events, and some people may find certain events stressful which others would see as a positive experience. Furthermore, individuals deal with stress and trauma in different ways; the presence of multiple risk factors does not necessarily imply that a person will become suicidal.

Depending on a person’s individual response, risk factors that may contribute to a person feeling suicidal include:

- Significant changes in:
– Relationships.
– Well-being of self or family member.
– Body image.
– Job, school, university, house, locality.
– Financial situation.
– World environment.
– Significant losses:
– Death of a loved one.
– Loss of a valued relationship.
– Loss of self esteem or personal expectations.
– Loss of employment.
– Perceived abuse:
– Physical.
– Emotional/Psychological.
– Sexual.
– Social.
– Neglect.

5. How would I know if someone I care about was contemplating suicide?

Often suicidal people will give warning signs, consciously or unconsciously, indicating that they need help and often in the hope that they will be rescued.These usually occur in clusters, so often several warning signs will be apparent. The presence of one or more of these warning signs is not intended as a guarantee that the person is suicidal: the only way to know for sure is to ask them. In other cases, a suicidal person may not want to be rescued,and may avoid giving warning signs.

Typical warning signs which are often exhibited by people who are feeling suicidal include:

– Withdrawing from friends and family.
– Depression, broadly speaking; not necessarily a diagnosable mental illness
such as clinical depression, but indicated by signs such as:
- Loss of interest in usual activities.
- Showing signs of sadness, hopelessness, irritability.
- Changes in appetite, weight, behavior, level of activity or
sleep patterns.
- Loss of energy.
- Making negative comments about self.
- Recurring suicidal thoughts or fantasies.
- Sudden change from extreme depression to being `at peace’ (may
indicate that they have decided to attempt suicide).
– Talking, Writing or Hinting about suicide.
– Previous attempts.
– Feelings of hopelessness and helplessness.
– Purposefully putting personal affairs in order:
- Giving away possessions.
- Sudden intense interest in personal wills or life insurance.
- `Clearing the air’ over personal incidents from the past.

This list is not definitive: some people may show no signs yet still feel suicidal, others may show many signs yet be coping OK; the only way to know for sure is to ask. In conjunction with the risk factors listed above, this list is intended to help people identify others who may be in need of support.
If a person is highly perturbed, has formed a potentially lethal plan to kill themselves and has the means to carry it out immediately available, they would be considered likely to attempt suicide.

6. I’m a bit uncomfortable about the topic; can’t it just go away?

Suicide has traditionally been a taboo topic in Western society, which has led to further alienation and only made the problem worse. Even after their deaths, suicide victims have often been alienated by not being buried near other people in the cemetery, as though they had committed some utterlyunforgivable sin.

We could go a long way to reducing our suicide rate by accepting people as they are, removing the social taboo on talking about feeling suicidal, and telling people that it _is_ OK to feel so bad that you’d think about suicide. A person simply talking about how they feel greatly reduces their distress; they also begin to see other options, and are much less likely to attempt suicide.

7. So what can I do about it?

There usually are people to whom a suicidal person can turn for help; if you ever know someone is feeling suicidal, or feel suicidal yourself, seek out people who could help, and keep seeking until you find someone who will listen. Once again, the only way to know if someone is feeling suicidal is if you ask them and they tell you.

Suicidal people, like all of us, need love, understanding and care. People usually don’t ask “are you feeling so bad that you’re thinking about suicide?” directly. Locking themselves away increases the isolation they feel and the likelihood that they may attempt suicide. Asking if they are feeling suicidal has the effect of giving them permission to feel the way they do, which reduces their isolation; if they are feeling suicidal, they may see that someone else is beginning to understand how they feel.

If someone you know tells you that they feel suicidal, above all, listen to them. Then listen some more. Tell them “I don’t want you to die”. Try to make yourself available to hear about how they feel, and try to form a “no-suicide contract”: ask them to promise you that they won’t suicide, and that if they feel that they want to hurt themselves again, they won’t do anything until they can contact either you, or someone else that can support them. Take them seriously, and refer them to someone equipped to help them most effectively, such as a Doctor, Community Health Centre, Counsellor, Psychologist, Social Worker, Youth Worker, Minister, etc etc. If they appear acutely suicidal and won’t talk, you may need to get them to a hospital emergency department.

Don’t try to “rescue” them or to take their responsibilities on board yourself, or be a hero and try to handle the situation on your own. You can be the most help by referring them to someone equipped to offer them the help they need, while you continue to support them and remember that what happens is ultimately their responsibility. Get yourself some support too, as you try to get support for them; don’t try to save the world on your own shoulders.

If you don’t know where to turn, chances are there are a number of 24 Hour anonymous telephone counselling or suicide prevention services in your area that you can call, listed in your local telephone directory. The crisis resource posting mentioned at the top of this posting also lists a number of Internet resources which provide support for people in crisis.

8. Help? Counselling? But isn’t counselling just a waste of time?

Certainly it is true that counselling is not a magic cure-all. It will be effective only if it empowers a person to build the sort of relationships theyneed for long-term support. It is not a “solution” in itself, but it can be a vital, effective and helpful step along the way.

9. Talk, talk, talk. It’s all just talk. How’s that going to help?

While it’s not a long-term solution in itself, asking a person and having them talk about how they feel greatly reduces their feelings of isolation and distress, which in turn significantly reduces the immediate risk of suicide. People that do care may be reluctant to be direct in talking about suicide because it’s something of a taboo subject.

In the medium and longer term, it’s important to seek help to resolve the problems as soon as possible; be they emotional or psychological. Previous attemptors are more likely to attempt suicide again, so it’s very important to get unresolved issues sorted out with professional help or counselling as necessary.
Some issues may never be completely resolved by counselling, but a good counsellor should be able to help a person deal with them constructively at present, and to teach them better coping skills and better methods of dealing with problems which arise in the future.

10. How do telephone counselling and suicide hot-line services work?

In an emergency, call the National Suicide Prevention Lifeline 1-800-273-TALK

Different services vary in what they offer, but in general you can ring up and speak anonymously to a counsellor about any sort of problem in a no-pressure context that’s less threatening than a face-to-face session. Talking the situation over with a caring, independent person can be of great assistance whether you’re in a crisis yourself, or worried about someone else who is, and they usually have connections with local services to refer you to if further help is required. You don’t have to wait until the deepest point of crisis or until you have a life-threatening problem before you seek help.
Demand for telephone services vary, so the most important thing to remember is that if you can’t get through on one, keep trying several until you do. You should usually get through straight away, but don’t give up or pin your life on it. Many people that feel suicidal don’t realize that help can be so close, or don’t think to call at the time because their distress is so overwhelming.

11. What about me; am I at risk?

It’s quite likely that some people that read this will one day attempt suicide,so here’s a quick suicide prevention exercise: think of a list of 5 people whoyou might talk to if you had no-one else to turn to, starting with the most preferred person at the top of the list. Form a “no-suicide contract” with
yourself promising that if you ever feel suicidal you will go to each of the people on this list in turn and simply tell them how you feel; and that if someone didn’t listen, you’d just keep going until you found someone that would. Many suicide attemptors are so distressed that they can’t see anywhere to turn in the midst of a crisis, so having thought beforehand of several people to approach would help.

12. How does suicide affect friends and family members?

Suicide is often extremely traumatic for the friends and family members that remain (the survivors), even though people that attempt suicide often think that no-one cares about them. In addition to the feelings of grief normally associated with a person’s death, there may be guilt, anger, resentment, remorse, confusion and great distress over unresolved issues. The stigma surrounding suicide can make it extremely difficult for survivors to deal with their grief and can cause them also to feel terribly isolated.
Survivors often find that people relate differently to them after the suicide, and may be very reluctant to talk about what has happened for fear of condemnation. They often feel like a failure because someone they cared so much about has chosen to suicide, and may also be fearful of forming any new relationships because of the intense pain they have experienced through the relationship with the person who has completed suicide.

People who have experienced the suicide of someone they cared deeply about can benefit from “survivor groups”, where they can relate to people who have been through a similar experience, and know they will be accepted without being judged or condemned. Most counselling services should be able to refer people to groups in their local area. Survivor groups, counselling and other appropriate help can be of tremendous assistance in easing the intense burden of unresolved feelings that suicide survivors often carry.

The suicide-survivors mailing list provides such a group via electronic mail. See the resource list companion posting mentioned at the top of this posting for more information.

13. Hang on; isn’t it illegal though? Doesn’t that stop people?

Whether it is legal or not makes no difference to someone who is in such distress that they are trying to kill themselves. You can’t legislate against emotional pain so making it illegal doesn’t stop people in distress from feeling suicidal. It is likely to merely isolate them further, particularly since the vast majority of attempts are unsuccessful, leaving the attemptor in a worse state than before if they’re now a criminal as well. In some countries and states it is still illegal, in other places it’s not.

14. But don’t people have the right to kill themselves if they want to?

Each of us is responsible for our own actions and life choices. In a sensethen, an individual may have the right to do as they wish with their life, including to end it if they so desire. Western societies in particular tend to emphasise individual rights over communal rights and responsibilities.

However, every person exists as part of a larger network of relationships of various types which set the context in which an individual’s rights and responsibilities exist. People who feel lonely, isolated, distressed and hopeless about their future can find it extremely difficult to recognise supportive relationships which may exist around them. This often causes them to grossly underestimate both the degree of support which could be gained from those around them, and the impact that their suicide would have should they complete it.

Discussions regarding rights can become emotive, particularly when there is a conflict between individual and communal rights and responsibilities. For example, people who have been emotionally devastated by the suicide of someone close to them could equally assert their right to not devastated by someone else’s suicide. It should be reiterated however that a person contemplating suicide is more likely to need understanding than a lecture on their responsibilities to other people.

Ultimately, helping people to deal with their problems better, see their options more clearly, make better choices for themselves and avoid choices that they would otherwise regret empowers people with their rights rather than taking their rights away.

The Sterankophile: A Photo of Young James

On the Reading Stand: "Brain Bugs" by Dean Buonomano

From the clearance book "to read" pile comes my latest, and just 25 pages in, it looks to be a winner.
Brain Bugs How the Brain’s Flaws Shape Our Lives by Dean Buonomano. The human brain is more beautiful and complex than anything we could ever build but it’s far from perfect. Our memory is unreliable; we can’t multiply large sums in our heads; advertising manipulates our judgment; we tend to distrust people who are different from us; supernatural beliefs are hard to shake and we prefer instant gratification to long-term gain.
       Dean Buonomano illuminates the causes and consequences of these "bugs" in terms of the brain’s innermost workings and their evolutionary purposes. He then goes a step further, examining how our brains function—and malfunction—in the digital, predator-free, information-saturated, special effects-addled world that we have built for ourselves. Along the way, this lively, surprising tour of mental glitches and how they arise gives us the tools to hone our cognitive strengths while recognising our inherent weaknesses.
"Brain Bugs is not only well written and researched, it also does a terrific job of explaining why we inevitably get many things wrong, and why we're brilliant at some things but hopeless at others." --   BBC Focus

" absolute delight to read and truly fascinating." -- Popular Science Blog

"Excellent...[Buonomano] reveals the intricate limitations and blessings of the most complex device in the known universe." -- The Atlantic

The human brain may be the best piece of technology ever created, but it’s far from perfect. Drawing on colorful examples and surprising research, neuroscientist Dean Buonomano exposes the blind spots and weaknesses that beset our brains and lead us to make misguided personal, professional, and financial decisions. Whether explaining why we are susceptible to advertisements or demonstrating how false memories are formed, Brain Bugs not only explains the brain’s inherent flaws but also gives us the tools to counteract them.

“[An] intriguing take on behavioral economics, marketing and human foibles.” (Kirkus Reviews )

"Writing a book about the hardware and software flaws of the human brain is an ingenious idea, and Buonomano has fully delivered on its promise. To a degree that is difficult for most of us to imagine, much less understand, our successes and failures, joys and sufferings, are the product of protein interactions and electrical changes taking place inside our heads. Brain Bugs is a remarkably accessible and engaging introduction to the neuroscience of the human condition." -- Sam Harris, author of the New York Times bestsellers The Moral Landscape, and The End of Faith
"In Brain Bugs, Dean Buonomano has brilliantly pulled off what few psychological scientists can do. In elegant and clear writing, he masterfully conveys the astonishing capability of the human mind, along with its flaws and limitations." -- Elizabeth Loftus, Distinguished Professor at the University of California, Irvine, and author of Eyewitness Testimony

"He takes readers on a lively tour of systematic biases and errors in human thinking, citing examples that are staples of psychology courses and other popular books. What is new, however, is Buonomano’s focus on the mechanisms of memory, especially its "associative architecture," as the main causes of the brain’s bugs." -- Christopher Chabris, New York Times

"What makes the book all the more compelling is the lucidity with which Buonomano recognizes, amidst its weaknesses, the brain's insurmountable strengths, feats artificial intelligence is ages from reaching--most notably, its remarkable penchant for pattern-recognition and what Buonomano calls "the inherent and irrepressible ability of the brain to build connections and make associations." -- Maria Popova, The Atlantic

"One of the things I liked most about this book was the way it leaps from neuron to brain and then to person and on to society and back again, making useful comparisons all the way." -- Susan Blackmore, Focus Magazine

Dean Buonomano is a professor in the Departments of Neurobiology and Psychology, and a member of the Brain Research Institute, and the Integrative Center for Learning and Memory at UCLA.

His research focuses on the neural basis of learning, neural computations, and how the brain tells time. His research has been funded by the National Institutes of Health and the National Science Foundation.
He has been interviewed about his research on timing and neural computation for Newsweek, Discover Magazine, Scientific American, Los Angeles Times, New Scientist, and The New Yorker.

Wednesday, May 1, 2013

BDNF Theory of Depression

Ketamine is a drug used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia, usually in combination with a sedative. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucinations, elevated blood pressure, and bronchodilation. Like other drugs of its class such as tiletamine and phencyclidine (PCP), it induces a state referred to as "dissociative anesthesia" and is sometime misused as a recreational drug.

Uncovering the Biology of Depression

by Jonathan Hwang, Yale Scientific, 2011

Professor of Psychiatry and Pharmacology Director at Yale University, Ronald Duman studies depression, a serious issue that affects approximately 17% of the U.S. population and is estimated to cost as much as $83.1 billion for our economy.

There is a general consensus in the scientific community that low levels of monoamine neurotransmitters are a major contributor of depression. From that belief, antidepressants are designed to increase levels of neurotransmitters in the brain. They block reuptake or breakdown of different types of neurotransmitters in order to maintain higher levels in the brain.

A diverse range of antidepressants exists. However, current antidepressants are still ineffective and have low response rates: only 1 in 3 respond to the first antidepressant treatment, and 2 in 3 ever respond after repeated treatments. Beyond knowing that antidepressants block or inhibit particular neurotransmitters, most scientists are still not sure which pathways these antidepressants influence and thus the types of mechanisms that contribute to depression. Duman’s work investigates these unknown pathways.

Neurotrophic Theory of Depression

The bulk of Professor Duman’s research has led to the formulation of the neurotrophic theory of depression, which states that neuronal growth factors contribute to the onset of depression. In 1995, Duman published a landmark paper relating increased brain derived neurotrophic factor (BDNF) levels with antidepressant effects, setting the foundation for the neurotrophic hypothesis of depression.

Since then, subsequent research has clarified the pathways leading to the expression of BDNF. Professor Duman’s research suggests that BDNF is expressed through the cyclic adenosine monophosphate (cAMP) signal transduction pathway, which is regulated by serotonin.

In this pathway, cAMP is first activated, and this leads to activation of cAMP dependent protein kinase, which regulates cAMP response to element-binding protein (CREB). Additionally, Duman found that long-term antidepressants increase levels of CREB mRNA and protein in the hippocampus, further supporting the link between antidepressants and the cAMP pathway. CREB seems to regulate a set of genes in the hippocampus producing antidepressant effects.

Stress reduces the complexity of density of dendrites (top) as compared to normal dendrites (bottom). Image courtesy of Duman.

The Role of BDNF

BDNF is a vital neurotrophic factor in the brain. Previous studies have shown that exposure to BDNF in the hippocampus can lead to increased strength in some synaptic connections. BDNF’s role in neurogenesis was of particular interest. Duman discovered that upregulation of neurogenesis was the result of several antidepressants, suggesting that antidepressants reverse the atrophy of neurons that occur during depression.

Other studies confirming Dr. Duman’s work have found that increasing levels of BDNF in specific areas of the brain, such as the hippocampus, leads to antidepressant effects. The hippocampus has been implicated in mood disorders and its connections to amygdala and the prefrontal cortex are important for the function of cognition and emotion. Additionally, studies by Duman also revealed the converse: loss of BDNF contributes to depression. Stress, a precursor of many mood disorders, also decreases expression of BDNF.

The approaches Professor Duman took to clarify BDNF’s role were varied. One was by using a viral vector to overexpress BDNF, which produced a behavioral phenotype typical of antidepressants. Antidepressant behavior was tested using the forced swim tests and learned helplessness models.

Another approach involved infusing recombinant BDNF into the brain region, which also produced a
similar antidepressant behavioral response. Duman also tested mice with a heterozygous deletion of the allele for BDNF. Although their phenotype appeared normal, they displayed a depressant-like phenotype once exposed to stress. This follows the widely held belief that a combination of environmental and genetic factors contributes to the onset of depression.

The mechanism regulating the expression of BDNF. Image courtesy of Duman.

A Faster and More Efficient Pathway

In August 2010, Duman’s lab discovered a completely new pathway, a major breakthrough for the field of depression. In ketamine, Duman addresses a pressing need in the field for “a more rapid, more efficient drug” to treat depression. In his paper published in Science, Duman lays the foundation for further understanding of this novel pathway.

Ten years ago, ketamine was preliminarily tested at the Connecticut Mental Health Center as an antidepressant in low doses. The subjects were patients who previously resisted all other forms of treatment, but over two thirds responded positively to ketamine. These results were confirmed in later studies. Much more remarkable about ketamine’s use as an antidepressant was how quickly the patients responded; antidepressant effects took place within two hours of treatment and lasted more than seven days.

“The story is in the pathway,” Duman explained. Unlike traditional antidepressants, which are generally neurotransmitter inhibitors, ketamine is a N-methyl-D-aspartic acid (NMDA) receptor antagonist.

It operates on an entirely different pathway from those of traditional neurotransmitters. Studies conducted by graduate student Nick Li demonstrate that ketamine activates the mammalian target of rapamycin (mTor) pathway. mTor is a ubiquitous protein kinase involved in protein synthesis and synaptic plasticity in a process called synaptogenesis.

Synaptogenesis restores the synapse connections in the brain that may deteriorate under stress and depression. The study also found increases in the levels of synapse proteins usually regulated by the mTor pathway. To physically confirm synapse formation, in collaboration with George Aghajanian, Professor of Psychiatry at Yale, two-photon imaging was used to observe increased spine density. Further supporting the link between the mTor pathway and antidepressant effects, Duman blocked the mTor pathway with rapamycin, leading to inhibition of ketamine’s antidepressant effects.

Ketamine is such a “magic drug” because it produces antidepressant effects in people who have resisted most other forms of treatment and its speed of response acts in days rather than weeks.

However, the key disadvantages of directly using ketamine as an antidepressant are its use as a street drug and its toxicity from repeated dosages. Despite these shortcomings, knowing the mechanisms of ketamine’s antidepressant effects will further benefit drug designs for immediate antidepressant effects.

Duman’s lab continues to further investigate factors and pathways for depression. One future direction is to deepen understanding of what stress does on a molecular scale and its link to depression. Other directions include studies to reveal more details about the mechanisms underlying Duman’s neurotrophic theory of depression. Professor Duman’s discoveries today could be the basis of depression treatments tomorrow.

Two-photon microscopy of neurons after treatment with ketamine (bottom) as compared to control (top) shows increased density. Image courtesy of Duman and Aghajanian.

About the Author

Jonathan Hwang is a Chemical Engineering major in Saybrook College.

The author would like to thank Professor Ronald Duman for his time and assistance over the course of writing this article.