Thursday, May 28, 2015

How Perpetrators Make Themselves the Vicitms: "Deny, Attack, and Reverse Victim and Offender" (DARVO)

http://2.bp.blogspot.com/-cSU4U35BiU0/U6cTb3kYFPI/AAAAAAAAAXM/munGnFt9_Ew/s1600/Blind-Betrayal-Ourselves-Arent-Fooled.jpg

It's a well-known feature of perpetrators that they generally deny what they have done, attack the accusers (often attempting to destroy their character), and then reverse the situation so that they claim to be the victims.

If you have any doubt about this, look closely at EVERY situation in which Marc Gafni has been accused of sexually inappropriate relationships with his students (often two or more at a time), which includes forcing them to lie about the relationships and controlling their contact with others outside his circle of trust.

Psychologist Jennifer J. Freyd, at the University of Oregon, has detailed this behavior in a model she calls DARVO = Deny, Attack, and Reverse Victim and Offender. What follows comes from her web page on this topic. Freyd is one of the world's experts on betrayal trauma.

Her books include:
Citation:
Freyd, J.J. (2014). What is DARVO? Retrieved 5.28.2015 from http://pages.uoregon.edu/dynamic/jjf/defineDARVO.html.

What is DARVO?

Jennifer J. Freyd, University of Oregon


Short Definition

DARVO refers to a reaction perpetrators of wrong doing, particularly sexual offenders, may display in response to being held accountable for their behavior. DARVO stands for "Deny, Attack, and Reverse Victim and Offender." The perpetrator or offender may Deny the behavior, Attack the individual doing the confronting, and Reverse the roles of Victim and Offender such that the perpetrator assumes the victim role and turns the true victim -- or the whistle blower -- into an alleged offender. This occurs, for instance, when an actually guilty perpetrator assumes the role of "falsely accused" and attacks the accuser's credibility or even blames the accuser of being the perpetrator of a false accusation. 
Disclaimers
  • DARVO as a concept is based on observation and analysis. The author has not completed systematic empirical research testing the coherence or frequency of DARVO. However, research is currently in progress in the author's laboratory at the University of Oregon.
  • Other observers have likely noted the same phenomena and related phenomena using different terms; the author has been informed that some people have found the term DARVO a helpful mnemonic and organizing concept.
  • Also the presence of DARVO is not necessarily evidence in support of the accusation of guilt; a truly innocent person may deny an accusation, attack the person making the accusation, or claim the victim role. Future research may be able to determine the probability of a DARVO response as a function of guilt or innocence. The author hypothesized that some sorts of denials and reactions such as DARVO are more likely when the perpetrator is guilty than innocent (Freyd, 1997); however this hypothesis has not yet been tested. Furthermore, even if research indicates that a DARVO reaction is more likely when there is actual guilt, it would be an error to use a DARVO reaction as proof of guilt.
  • For now the concept of DARVO is offered as potentially memorable and useful term for anticipating the behavior of perpetrators when held accountable, and for making sense of responses that may otherwise be confusing (particularly when victim and offender get reversed). Research is needed.
History of Terminology & Writings about DARVO

Jennifer Freyd introduced the term "DARVO" near the end of a 1997 publication about her primary research focus, "betrayal trauma theory." (For more on betrayal trauma theory, see http://pages.uoregon.edu/dynamic/jjf/defineBT.html.)

The reference for the 1997 article introducing the term is:

Freyd, J.J. (1997) Violations of power, adaptive blindness, and betrayal trauma theory. Feminism & Psychology, 7, 22-32.
In that paper Freyd explained that DARVO responses may be effective for perpetrators. "...I have observed that actual abusers threaten, bully and make a nightmare for anyone who holds them accountable or asks them to change their abusive behavior. This attack, intended to chill and terrify, typically includes threats of law suits, overt and covert attacks on the whistle-blower's credicility, and so on..... [T]he offender rapidly creates the impression that the abuser is the wronged one, while the victim or concerned observer is the offender. Figure and ground are completely reversed... The offender is on the offense and the person attempting to hold the offender accountable is put on the defense." (Freyd, 1997, p 29-30)

These ideas were further developed in an article by Veldhuis and Freyd (1999):

Veldhuis, C. B., & Freyd, J. J. (1999). Groomed for silence, groomed for betrayal. In M. Rivera (Ed.), Fragment by Fragment: Feminist Perspectives on Memory and Child Sexual Abuse (pp. 253-282). Charlottetown, PEI Canada: Gynergy Books.
In the 1999 article Veldhuis and Freyd explore the separate components of DARVO, and they also note a connection between DARVO and "betrayal blindness," a concept from betrayal trauma theory (Freyd, 1996).
"By denying, attacking and reversing perpetrators into victims, reality gets even more confusing and unspeakable for the real victim. .... These perpetrator reactions increase the need for betrayal blindness. If the victim does speak out and gets this level of attack, she quickly gets the idea that silence is safer." (Veldhuis & Freyd, 1999. p 274).
Since then the concept of DARVO has appeared in various writings, the most significant of which is our new book Blind to Betrayal (Freyd & Birrell, 2013).

 
Blind to Betrayal: Why We Fool Ourselves We Aren't Being Fooled

In Blind to Betrayal we urge institutions to cherish the whistle blower (see p. 173) and we offer suggestions for specific steps institutions can take to prevent and repair institutional betrayal. In Blind to Betrayal we also talk about institutional denial which plays such a crucial role in instutional betrayal. DARVO is a particularly pernicious form of denial (see p 119 of Blind to Betrayal).
Two Common Types of Denial

Two common forms of perpetrator (or bystander) denial are:

  1. It didn't happen (an instance) or It rarely happens (a type of event)
  2. It wasn't harmful
Put together they can take the form: "It didn't happen, but if it did, it wasn't that bad" or "It rarely happens, but when it does it isn't harmful." The two claims both serve to deny, but they depend upon different sorts of evidence. They may both be true, but they are sometimes somewhat suspicious when claimed simultaneously (or by the same person at different times), as for instance can occur in response to allegations of rape or child sexual abuse.

Wednesday, May 20, 2015

Arthur Gillard Interviews the Creators of the SF / Lucid Dreaming Web Series "Anamnesis"

http://www.world-of-lucid-dreaming.com/image-files/anamnesis-the-lucid-dreaming-web-series.jpg

The following is a guest post from my friend Arthur Gillard. He recently interviewed the creators of the science fiction/lucid dreaming web series, Anamnesis. Here is a brief synopsis of the series, from the website:
When a woman dreams of her boyfriend’s death on the same night he’s murdered, she and a group of strangers begin to unravel a greater mystery by journeying into their subconscious.
An abbreviated version of this interview will appear soon in Lucid Dreaming Experience, a free online journal.

Enjoy the FULL interview!

Photo original

* * * * *

Interview with the Creators of the SF/ Lucid Dreaming Web Series Anamnesis by Arthur Gillard

Anamnesis is a science fiction web series about lucid dreaming based on an original short film of the same name. It has been getting a great deal of positive attention in the lucid dreaming community based on its accurate and realistic portrayal of lucid dreaming, as well as its compelling storyline, good acting, professional production values, and gorgeous cinematography. I had a chance recently to interview Alex Calleros, writer and director of the original short, and Michael Tucker, who co-wrote and co-directed the web series with Alex. 

The following interview may contain some spoilers, so I recommend watching the original short and the five episode web series before reading the interview. You can see the original short here, and the web series here. Altogether it takes a little over an hour to watch. 

You can find out more about the series by following them on Google Plus, Twitter [@AnamnesisSeries], or Facebook, or via email at info@finite-films.com

(Disclosure: I've agreed to manage the Anamnesis Google Plus page on a volunteer basis, without compensation.)

Arthur Gillard: Why did you decide to make a film/web series about lucid dreaming? Was it inspired by your own experiences with lucidity, or did you simply find the subject intriguing?

Alex Calleros: I’ve always been intrigued by the relationship between cinema and dreams. The experience of watching a film is often thought of as entering a sort of dream-state, and many of my favorite films play with questions of reality, consciousness, etc. The Matrix, Inception, Eternal Sunshine of the Spotless Mind—these films were huge influences for me as a filmmaker and I had always wanted to play in the world of dreams using cinema. So, when I had the opportunity to write and direct the short film in 2012, it was a chance to finally make a film that essentially takes place entirely in the dream world. One of my favorite films is The Fountain, which explores the theme of death in an incredibly profound way, and that was also a huge influence on the short film.

Michael Tucker: When we began thinking of how to continue the short film (which has a pretty definite conclusion), we played around with a lot of ideas. Alex’s close friend Gary Ruiz was very into lucid dreaming and had talked to Alex about it. The idea of becoming lucid within a dream world and being able to manipulate your surroundings fascinated us and seemed like a great concept to play with cinematically, as well as an idea we hadn’t seen done before. So we spent time researching lucid dreaming techniques and experiences, and grew attached to the idea of trying to portray the sensation of dreaming as accurately as possible. We didn’t want it to be blurry and fuzzy like how dreaming is often shown in TV shows, but we also didn’t want it to be as rigid and straight-forward as Inception. So finding that balance was our guiding light, and hopefully we achieved that to some degree.

Arther: Could you explain the meaning of the word “anamnesis,” and how that relates to the themes explored in the series and the original short film?

Alex: The Google definition of anamnesis is:
1) recollection, in particular
2) the remembering of things from a supposed previous existence

I first discovered the word being used in a philosophical / spiritual context—anamnesis was used to describe the process of “awakening to” or “remembering” one’s true nature or identity. The original short film explores the theme of identity—who are you, really? That’s the question being asked of the main character, Adam, throughout the short. His process of remembering what he had forgotten forms the arc of the story, and I thought the word “anamnesis” represented that arc perfectly.

Arthur: How does the web series relate to the original short? Is it a straightforward continuation, or is it more like a reboot, a variation on a theme?

Michael: We wanted the web series to stand on its own for anyone who hadn’t seen the original short, but we also wanted people that had seen the short to be able to watch it as a continuation. So even though stylistically-speaking there are differences between them, story-wise we tried to make it as directly connected as we could.

Arthur: I understand that lucid dreaming expert and author Daniel Love consulted on the show. How did he get involved, and how closely did he work with you? Did he review scenes in the script and suggest changes? Did he suggest any details or scenes to include?

Michael: Daniel Love contacted us after he stumbled upon our Kickstarter campaign. He had just finished his book on lucid dreaming, “Are You Dreaming?” and sent us free copies to check out. We also took him up on his offer to look over the scripts as we were finalizing them, and he made several suggestions of how to tweak things so that they would be more accurate. He explained some reality tests that we hadn’t heard of, and helped us pinpoint exactly where and when the characters might use them. And since the series has released, he’s connected us with a lot of the lucid dreaming community, which has been amazing. So overall Daniel Love was a really big help.

Arthur: Who among the cast and crew of Anamnesis is a lucid dreamer? Could you share some of your own lucid dreams? Please go into as much detail as you are willing. To what extent did lucid dreams of the cast and crew influence how dreams are portrayed? Did working on Anamnesis influence your dreams?

Alex: Brad C. Wilcox, who plays Noah, had frequent lucid dreams for a period of his life. In fact, they had gotten so constant that he had to “cut back,” as he wasn’t feeling properly rested in the morning.

Michael: Zach Brown plays Sean, the show’s expert lucid dreamer. To prepare for the role, Zach researched lucid dreaming and practiced it in his daily life. He would actually draw the letter “A” on his hand, as Sean does in the show, as a reminder to ask himself, “Am I awake?” He told us about a lucid dream he had in which Whoopi Goldberg was his dream guide. It sounded pretty awesome.

Alex: I had a really striking wake-induced lucid dream during the production of Anamnesis. I had woken up extra-early one morning, and as I was falling back asleep I managed to maintain awareness. I’ll never forget the moment I passed into the dream state: all at once, I felt my body launch off the bed and hover for a moment near the ceiling of my bedroom. I passed through some sort of portal and found myself floating above the swimming pool in my childhood backyard in Arizona. I didn’t really have any control over what was happening; I was just along for the ride. My dream body plunged into the pool, where I was delighted to find I could breathe underwater. I looked up and watched in awe as raindrops created thousands of intricate ripples on the surface of the water. A red Arizona dust storm colored the sunlight filtering into the water. It was one of the most vibrant, beautiful visions I’ve ever had...so beautiful that I got excited and promptly woke up. But that one really stuck with me.

Michael: The only lucid dream that I can for sure say was me becoming lucid happened during the midst of shooting the series. Between researching lucid dreaming, and writing the scripts, and then filming all the scenes, all of that information was swirling around in my head all the time. In my dream, I was in my high school cafeteria, looking around, when suddenly I remembered one of the reality tests that the character Hannah does in the show. She pinches her nose with her fingers in such a way that she shouldn’t be able to breathe in—but she can. So I thought, “eh, may as well give it a try and see what happens.” So I pinched my nose and then breathed in—and it worked! I suddenly realized I was dreaming, and immediately did a slow-motion backflip into the air and started to fly. I remember I knew exactly how to control my body in flight, how to turn, spin, everything. Unfortunately I became really overwhelmed by the excitement of it all. I tried to calm myself down so I wouldn’t wake up, but it was all too much and I woke up almost immediately after I started flying. It was a pretty awesome experience.

Arthur: I found the original short film particularly moving. The repeated inquiries into Adam's true identity and the suggestion that he was now “who he had always been” were suggestive and yet open to interpretation by the viewer—almost like a Zen koan, inviting a deeper look at one's own ultimate identity. Did any particular spiritual tradition or school of thought inform the original short film?

Alex: We made the short film as part of this year-long project where we asked our audience to send us 1-sentence constraints that we’d have to follow in our next film. One of the constraints for Anamnesis was: “The dialogue from one scene must be exactly the same in one scene as it is in another,” which fortuitously led to the idea of posing this question “Who are you?” to Adam throughout the movie. I definitely wanted to tap into a “Zen koan” feel with those repeated inquiries. Only at the end does he understand the at-first puzzling answer, “You’re who you’ve always been.”

Over the past several years, I’ve been really interested in Western-born philosophers who take the deep wisdom embedded in Eastern religions (Buddhism in particular) and translate/update them for the modern age. Alan Watts was one of the first to do this in the 50’s and 60’s, and hundreds of audio recordings of his wonderful lectures are widely available online today. Listening to him speak is both enlightening and incredibly fun (he’s got a delightful British accent and a sharp sense of humor). I’m also very interested in the work of American philosopher Ken Wilber, who has pioneered a movement to see the world “integrally,” integrating the truths of science, psychology, art, spirituality, etc. I believe I actually discovered the word “anamnesis” while reading an article by Wilber.

Arthur: In the original short, Hannah is seemingly portrayed as a powerful lucid dreamer, for example creating portals from one dream scene to another. “I know my way around in here,” she remarks to Adam at one point. In the series, it's less clear that she's lucid dreaming. Based on the short film I see her in the series as dreaming lucidly, probably assuming that Sean is a character in her dreams. Is that an accurate interpretation? Will we see Hannah coming forth again as a powerful lucid dreamer in her own right in future episodes?

Alex: I’ll be honest, when we made the short film, we weren’t even sure Hannah was a “real” character or simply a figment of Adam’s imagination fashioned after his memory of Hannah. Once we had the opportunity to create a web series based on the short, we came up with the premise that it was actually the real Hannah, and that she was somehow sharing a dream with Adam.

All that said, I’d argue that Hannah wasn’t particularly lucid in the short film. She “knew her way around” and kind of went with the flow, but really it was Adam’s subconscious driving the whole dream forward, she was just along for the ride. When she wakes up in Episode 01 of the web series, Hannah has a very foggy memory of the dream, and only remembers it in flashes when she comes across dream signs in her waking life (the water glass spilling, the copy shop, etc.), which further suggests she wasn’t fully lucid.

The first time I think Hannah actually becomes lucid in the series is Episode 04, when Sean calls to her attention that they’re in a dream and teaches her about reality tests. In a lot of ways, the long-term trajectory we see for the characters in Anamnesis is a journey from being “asleep” to becoming “lucid” or “awake”—in more ways than one.

Arthur: I've recently finished re-reading Patricia Garfield's excellent book The Dream Messenger: How Dreams of the Departed Bring Healing Gifts, which explores the various kinds of dreams people have after a loved one has died, and the role such dreams play in the healing process. This seems like a rich potential territory to explore in Anamnesis. Might Adam start showing up in Hannah's or Vera's dreams in future episodes?

Alex: We’ve definitely talked about this as a possibility. We’d love to bring Adam back in some fashion. If Hannah continues to become more lucid in the dream world, it’s kind of inevitable that he’ll show up in some form or another.

Arthur: Is there any significance to the names of the characters? “Vera,” for example, reminded me of veritas, truth, the idea that “the truth shall set you free.” She certainly seems happy to break rules in an attempt to uncover the truth.

Michael: In general we didn’t choose the character names specifically because of their meanings. For the most part, we based it on which names sounded good and felt like they matched the characters. Vera is a name I’ve always liked, both because of how it sounds and because of its meaning, and I think it fits Vera’s character really well for exactly the reason you mentioned. Noah’s name is also an obvious reference, but that wasn’t the only reason we chose it for him. We love it when elements of a story can have deeper meanings, but I also think you can go overboard with that to the point that it’s hitting the audience over the head with it. Inception, for instance, is not subtle at all when it comes to character names having deeper meanings—which while cool, I found more distracting than anything else.

Arthur: Whereas the original short is completely self-contained, the series continues to get more complex and mysterious episode-by-episode, leaving the viewer hungry for more. Are you planning to make more episodes? If so, do you have an overall story arc in mind for the show? Can you say anything about specific ideas or themes you'd like to explore in future episodes?

Alex: When we were brainstorming what we wanted to do with the web series, one of our main inspirations was Lost, which unraveled an incredibly intricate mystery over several seasons. We wanted to see if we could pull off the same kind of science-fiction mystery in the world of lucid dreaming—but actually know where it was all going, from the very first episode. So yes, we definitely have an overall story arc in mind for the show. It will probably change and evolve if we get to make more episodes, but there are clues hidden as early as Episode 01 as to what’s coming next.

Arthur: You explore a number of dream themes in the series—lucid dreaming, of course, but also night terrors and out-of-body experiences. In future episodes, do you plan to explore a greater variety of dream and dreamlike states, such as false awakenings, sleep paralysis, hypnagogia?

Michael: If we get to make more episodes we would absolutely want to explore more of these dream / dreamlike states. I get excited about there being so many interesting experiences to be played with, that they all lend themselves so well to film. The medium of film can convey the dream experience better than any other, in my opinion, and we have a lot of fun as filmmakers coming up with ways to translate these dream experiences to the screen. In particular, I find the idea of sleep paralysis terrifying...so it’d be fun to play with that on screen.

Arthur: The first season of Anamnesis was made possible through a highly successful Kickstarter campaign, in which you raised 151% of the money you were asking for. If you make more episodes, how do you plan to finance them? How can fans of the series support you in making more episodes?

Michael: Figuring out how to finance more episodes is the main challenge we’re facing right now. It blew us away that we surpassed our funding goal on Kickstarter, and we combined that with funding from FilmSkillet.com, whose founder, Jeremy Norris, reached out to us and essentially convinced us to make the web series in the first place. But even with these combined funds, Anamnesis was primarily a labor of love. We didn’t have enough to pay most of the cast and crew, and almost all of the money went to locations, food, and equipment rentals.

If we were to make more, we would have to be able to pay all the cast and crew for the excellent work that they do. And considering the first five episodes are about 70 minutes long, each season is essentially a feature film. So we would need the budget of an indie feature film. Crowdfunding a next season would definitely be an option, but we’re also trying to reach out to websites like Vimeo, for example, who are getting into the original content market. Having a distributor for the series that could also help fund another season would be absolutely great. So the best thing fans can do to help us make more episodes is share the series with anyone and everyone. The more we can show that we have a large group of dedicated fans, the more likely we can raise money via crowdfunding and the easier it would be to convince a potential distribution partner.

Arthur: What do you think of YouTube's plan to start offering an ad-free subscription service? How might that affect Finite Films?

Michael: I understand that YouTube has been trying to figure out how to make a profit since they first began, but this feels somewhat like a betrayal of what has made YouTube so popular in the first place. There is a freedom and accessibility that YouTube has (which admittedly comes with some chaos and a lot of junk) that I think may be tainted by a subscription fee. Especially if they keep forcing unskippable ads onto every video to make the viewing experience more unpleasant in order to convince people to pay the subscription fee.

On the other hand, if it means that they’re helping content creators like ourselves get something more out of it (financially speaking), then perhaps they’re incentivizing and enabling people to make more quality content. Ultimately I think it will depend largely on how much the subscription fee is, and how optional they make it feel. If it’s $2.99 a month, maybe that’s an okay deal that feels worthwhile; if it’s $19.99 a month and every YouTube video has a 2-minute unskippable ad—then I think that will be bad for views, for content creators, and for YouTube. I guess we’ll just have to wait and see.

Arthur: What has been the reaction of the lucid dreaming community to Anamnesis? How do people without prior experience with lucid dreaming react to the show?

Alex: Honestly, we’ve been blown away by the reception we’ve had in the lucid dreaming community. We wanted Anamnesis to represent the experience of lucid dreaming in a more accurate way than we’d seen in other films and TV shows, and so to have such a positive response from the community has been incredible. Our fans in the lucid dreaming community really are the primary reason we want to find a way to finance and produce more episodes. We’ve also had great responses from our non-lucid-dreamer fans, and we’re now looking to try to expand our audience beyond the lucid dreaming niche into communities that value thoughtful science fiction / drama storytelling.

Arthur: Are there any particular resources—books, websites, etc.—that you would recommend to people wanting to more deeply explore lucid dreaming?

Alex: Are You Dreaming by Daniel Love provides a great introduction to the world of lucid dreaming. He developed the CAT (Cycle Adjustment Technique) for generating frequent lucid dreams, which he outlines in his book. Our friend Jay Mutzafi (aka Lucid Sage and host of The Lucid Dreaming Podcast) highly recommends Stephen LaBerge’s Lucid Dreaming: AConcise Guide to Awakening in Your Dreams and in Your Life as a great place to start one’s lucid dreaming practice. And finally, www.world-of-lucid-dreaming.com has a ton of resources for anyone looking to lucid dream.

Arthur: Thank you for producing such an excellent short film and web series, and in particular for the realistic portrayal of lucid dreaming. I wish you great success and will certainly be doing my part to help spread the word. Is there anything we haven't covered in the interview that you would like to add?

Alex: We’ve had a lot of people ask us if they can buy Season One of the series on DVD, and we’re currently putting together a DVD / Digital Download package that will include some exclusive special features. For updates on all things Anamnesis, people can follow us on Facebook, Twitter [@AnamnesisSeries], and Google Plus (and subscribe to our channel, Finite Films, on YouTube).

From the very beginning, Anamnesis has been a true labor of love and we’ve only made it this far because of the support of our fans. If anyone has any ideas or suggestions for how we can continue to reach out to the lucid dreaming community and rally support for future seasons, don’t hesitate to shoot us an email at info@finite-films.com.

Saturday, April 11, 2015

George Lakoff: How Brains Think: The Embodiment Hypothesis


Published on Apr 7, 2015

Keynote address recorded March 14, 2015 at the inaugural International Convention of Psychological Science in Amsterdam.

Saturday, 14 March 2015


George Lakoff
Departments of Linguistics and Cognitive Science, University of California, Berkeley, USA
How do we answer the question, “How are thought and language constituted by the brain’s neural circuitry?” Neuroscience alone cannot answer this question. The field that studies the details of embodied conceptual systems and their expression in language is cognitive linguistics. In a book (in preparation with Srini Narayanan) we propose a neural computational “bridging model” as a way to answer the question. The talk gives illustrative details.

George Lakoff is a world-renowned cognitive linguist whose work reaches beyond the area of linguistics to provide groundbreaking insights into the realms of neuroscience and cognitive psychology as well. He is a pioneer in the multidisciplinary theory of the embodied mind, the idea that higher-order aspects of cognition are rooted in and constrained by bodily features such as the motor and perceptual systems. Additionally, his metaphor theory and insight into morally based framing, in which ideas are conveyed using very specific language that is tied to a larger conceptual framework such as freedom or equality, have made him a go-to strategist for politicians.
Read more about George Lakoff.

Books by George Lakoff that might be of interest.


Metaphors We Live By (2003, updated reissue)
Where Mathematics Comes From: How The Embodied Mind Brings Mathematics Into Being (2000)
Philosophy in the Flesh: the Embodied Mind & its Challenge to Western Thought (1999)

Friday, March 27, 2015

2014 Nobel Prize Winners Speak at the University of Arizona

Thursday afternoon, Edvard Moser, May-Britt Moser, and John O'Keefe, the three 2014 Nobel Prize winners for Physiology or Medicine, along with Eleanor Maguire, the winner of the 2003 Ig Nobel Prize for her "London taxi driver" study on hippocampal plasticity, spoke at a public forum at the University of Arizona.

Maquire's research on London taxi drivers, before and after going through two to three years of training required to learn and memorize 25,000 streets, revealed that their hippocampus grew as they memorized London's maze of streets. This was one of the first studies that demonstrated hippocampal neuroplasticity. She was awarded a 2003 Ig Nobel Prize for this study.

According to Improbable Research, the bestowers of the Ig Nobel Prize, "The Ig Nobel Prizes honor achievements that make people LAUGH, and then THINK. The prizes are intended to celebrate the unusual, honor the imaginative — and spur people's interest in science, medicine, and technology."

The Mosers and O'Keefe won their Nobel Prize in 2014 for their discoveries of specialized cells in the brain that together act as a navigation system. The Mosers discovered neurons that function as grid cells, found in the entorhinal cortex, while O'Keefe discovered neurons that function as place cells, found in the hippocampus.
"All memories are attached in some way to where you are, and in that way, the hippocampus acts as an anchor for remembering yourself within your experience," said Carol Barnes, Regents' Professor in the Departments of Psychology, Neurology and Neuroscience, the Evelyn F. McKnight Endowed Chair for Learning and Memory in Aging.
The hippocampus, according to Wikipedia, "belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation." If a person were to suffer severe damage to the hippocampus (both hippocampi, as one exists in each brain hemisphere), it's likely they may acquire anterograde amnesia, an inability to form and/or retain new memories (episodic or autobiographical memory, which are forms of declarative memory). In Alzheimer's Disease, the hippocampus is one of the first brain regions to experience damage, resulting in the disorientation and loss of recognition so common in the disease. However, damage to the hippocampus does not inhibit the ability to learn new skills, such as riding a bicycle (procedural memory).
 
 Spatial firing patterns of 8 place cells recorded from the CA1 layer of a rat. The rat ran back and forth along an elevated track, stopping at each end to eat a small food reward. Dots indicate positions where action potentials were recorded, with color indicating which neuron emitted that action potential. [via Wikipedia]
Below, I have included the honored guests as well as the first half of the press release about the public forum (which is heavy on the U of A is awesome rhetoric).
Guests

Edvard Moser
, Professor and Director, Kavli Institute of Systems Neuroscience; Co-Director, Centre of Neural Computation, Norwegian University of Science and Technology


May-Britt Moser, Professor and Director, Centre of Neural Computation; Co-Director, Kavli Institute of Systems Neuroscience, Norwegian University of Science and Technology

The Moser’s received the 2014 Nobel Prize in Medicine or Physiology (along with J. O’Keefe) for this discovery of grid cells.

John O’Keefe, Professor, Institute of Cognitive Neuroscience and Department of Anatomy, University College London. Dr. O’Keefe received the 2014 Nobel Prize in Medicine or Physiology (along with the Moser’s) for his discovery of place cells.

Eileen O’Keefe
(John’s wife), Emeritus Professor, Public Health, London Metropolitan University


Eleanor Maguire, Professor of Cognitive Neuroscience, University College Dublin Dr. Maguire received the 2003 Ig Nobel Prize for Medicine for her ‘London taxi driver’ student on hippocampal plasticity.
And here is the beginning of the press release . . . 

Nobel Laureates Say UA Scientists Paved Way

By Daniel Stolte, University Relations - Communications | March 27, 2015
 
UA researcher Carol Barnes says the new Center for Innovation in Brain Science will serve as a hub of transdisciplinary research. (Photo: John de Dios/UANews)
UA researcher Carol Barnes says the new Center for Innovation in Brain Science will serve as a hub of transdisciplinary research. (Photo: John de Dios/UANews)

 Four internationally renowned brain scholars visit campus and describe the UA as "one of the centers of neuroscience." The new Center for Innovation in Brain Science will foster transdisciplinary research, with the goal of better diagnostics and treatments for disorders such as Alzheimer's disease.

Nobel Prize laureate John O'Keefe, with May-Britt Moser (left) and Eleanor Maguire, says the UA's Carol Barnes "has told us as much about how the brain ages as anyone else." (Photo: John de Dios/UANews)

Take it from several Nobel laureates: Brain researchers at the University of Arizona are poised to make important contributions to finding better diagnoses and possibly treatments for brain disorders such as Alzheimer's disease.

To help commemorate three milestones in brain science research at the UA, four internationally renowned brain scholars — including three who shared the latest Nobel Prize in Physiology or Medicine — visited the UA campus this week to speak about their scientific careers and reflect on the tight connections they have shared with UA colleagues over many years.

This year marks the 25th anniversary of the UA Arizona Research Laboratories Division of Neural Systems, Memory and Aging, or NSMA; the 10th anniversary of the Evelyn F. McKnight Brain Institute at the UA; and the fifth anniversary of the UA School of Mind, Brain and Behavior.

UA President Ann Weaver Hart has named neuroscience as a research priority under the UA's strategic Never Settle plan. The BIO5 Institute and the UA Health Sciences Center have goals of supporting transdisciplinary neuroscience research in partnership with institutions across the state — from the molecular underpinnings of brain-cell health to the translation of this biological knowledge into treatments for neurological disease. The College of Science and the Office for Research and Discovery also are involved in supporting these efforts through the School of Mind, Brain and Behavior; NSMA; and the Evelyn F. McKnight Brain Institute.

During a public forum on Thursday, the UA welcomed the four guests to share their stories of discoveries in neuroscience with UA students, members of the public and the media. The visitors were John O'Keefe and Edvard and May-Britt Moser, who shared the 2014 Nobel Prize in Physiology or Medicine, and Eleanor Maguire, who received the Ig Nobel Prize for Medicine in 2003.

O'Keefe and the Mosers received the prize for their discoveries of specialized cells in the brain that together act like a navigation system.

"All memories are attached in some way to where you are, and in that way, the hippocampus acts as an anchor for remembering yourself within your experience," said Carol Barnes, who organized the visit along with two other UA brain researchers: Lynn Nadel, a Regents' Professor of Psychology and Cognitive Science and chair of the UA faculty; and Mary Peterson, professor of psychology and chair of the School of Mind, Brain and Behavior executive committee; director of the Cognitive Science Program; and chair of the Cognitive Science Graduate Interdisciplinary Program.

Edvard Moser said that some important work leading up to the Nobel Prize was done at the UA — for example, developing the technology for recording the activity of many brain cells at the same time, and developing ideas of how memory is generated in the hippocampus.

"The UA is one of the centers of neuroscience," O'Keefe said. "As one of the world's experts on the aging brain, Carol has told us as much about how the brain ages by looking at the hippocampus as anyone else.
Read the whole report on the event.

Friday, March 06, 2015

SSRIs Add to the Existing Surplus of Serotonin in the Raphe Nucleus and Reduces Serotonin in Hippocampus, Where it Is Needed Most

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This appears to be the first good research showing why SSRIs do not work for most people in treating depression and anxiety. It appears that early life stress increases serotonin levels in the brain to the point that a negative feedback loop develops, reducing the brain's sensitivity to the serotonin. The resulting depression and/or anxiety that develops is exacerbated by SSRIs, which just add to the existing surplus of serotonin in the raphe nucleus and reduces serotonin in hippocampus, where it is needed most.

Early life stress may cause excess serotonin release resulting in a serotonin deficit

Data suggest a reason why SSRI medications may fail in many patients
 
Studies indicate that the majority of people with mood and anxiety disorders who receive the most commonly prescribed class of antidepressant medications, Selective Serotonin Reuptake Inhibitors or SSRI's, are not helped by these medications. SSRIs are designed to increase serotonin, a neurotransmitter in the brain that is key to maintenance of mood. 

Researchers led by Jeremy D. Coplan, MD, professor of psychiatry at SUNY Downstate Medical Center, have published data suggesting an explanation for the longstanding puzzle as to why low serotonin could not be detected in depression without suicidal intent, even though many antidepressant treatments work by increasing serotonin in areas key for mood regulation, such as the hippocampus. The pre-clinical research was published in a recent edition of Frontiers in Behavioral Neuroscience.
 
Dr. Coplan explains, "We have shown that serotonin is too high near the serotonin brain cells, reducing firing of the serotonin nerve cells through a well-documented negative feedback mechanism in the raphe nucleus. The result is that the hippocampus and other critical brain structures needed for mood maintenance do not get enough serotonin. We can see this because the hippocampus is shrunken and the white matter loses integrity. By the time serotonin metabolites are measured in a lumbar spinal tap, the usual way serotonin levels have been measured, the high serotonin has mixed with the low serotonin and you have no difference from people who are healthy." 

He continues, "We have hypothesized in an earlier paper that this is a plausible reason why SSRIs may not work in a majority of people, because SSRIs will tend to make the high serotonin even higher in the raphe nucleus. The serotonin neuron may not be able to adapt and restore its firing, inducing a presumed serotonin deficit in terminal fields, evidenced by shrinkage of the hippocampus." 

He adds, "We cannot say categorically, in our pre-clinical model, that high serotonin in the raphe nucleus leads to low serotonin in the hippocampus, but studies by J. John Mann, MD, a co-author on the paper, and Victoria Arango, PhD, both of Columbia University Medical Center, have shown that people who committed suicide exhibited high serotonin in the raphe nucleus and low serotonin in another area of the brain critical for mood maintenance, the prefrontal cortex. Additional studies should be performed, especially since better understanding of the serotonin system will significantly improve future treatment options." 

In the earlier paper, also in Frontiers in Behavioral Neuroscience, Dr. Coplan proposed augmentation therapies in treatment-resistant patients, including stacking one medication upon another in the most difficult cases: "This is what physicians do for hypertension, diabetes, and congestive heart failure," said Dr. Coplan. "But in psychiatry, we sometimes act as if our medications are so effective that we are exempt from how the rest of medicine deals with difficult-to-treat cases." 

Other approaches to bypass the high midbrain serotonin impasse, according to Dr. Coplan, are shutting glutamate input into the raphe nucleus, a portion of the brain that controls the release of serotonin, and utilizing drugs that block noradrenergic input into the dorsal raphe. 

Dr. Coplan notes that a recent large-scale study showed only a minority of patients do well on SSRIs, and of those, many lose response in a year or two. "There is an epidemic of inadequately treated depression and psychiatrists are not well trained to deal with this challenge," he observed. "What they often do is change from one antidepressant to another when there is a lack of response. Eventually the patient becomes non-compliant and the patient, rather than the treatment, is blamed for the non-efficacy." 

"These two papers provide possible insights as to why our treatments are ineffective and what we should be doing to treat patients effectively," Dr. Coplan said. "Many academic researchers currently do not practice clinically, so they are out of touch with real-life patients and their struggles. In the meantime, suicide rates have not budged in decades." 
Here are the abstracts from the original articles, both of which are open access.

Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function in mood and anxiety disorders


Jeremy D. Coplan1*, Sasha L. Fulton2, Wade Reiner3, Andrea Jackowski4, Venkatesh Panthangi1, Tarique D. Perera2, Jack M. Gorman5, Yung-yu Huang6, Cheuk Y. Tang7, Patrick R. Hof8, Arie Kaffman9, Andrew J. Dwork6, Sanjay J. Mathew10,11, Joan Kaufman12 and J. John Mann6

  • 1Nonhuman Primate Laboratory, Department of Psychiatry and Behavioral Sciences, Downstate Medical Center, State University of New York, Brooklyn, NY, USA
  • 2Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY, USA
  • 3College of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA
  • 4Departamento de Psiquiatria & Neuroradiologia, Universidade Federal de São Paulo, São Paulo, Brazil
  • 5Franklin Behavioral Health Consultants, Bronx, NY, USA
  • 6Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA
  • 7Departments of Psychiatry, Neuroscience, and Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 8Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 9Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
  • 10Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, TX, USA
  • 11Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
  • 12Child Study Center, Yale University School of Medicine, New Haven, CT, USA

Background: Early life stress (ELS) is cited as a risk for mood and anxiety disorders, potentially through altered serotonin neurotransmission. We examined the effects of ELS, utilizing the variable foraging demand (VFD) macaque model, on adolescent monoamine metabolites. We sought to replicate an increase in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) observed in two previous VFD cohorts. We hypothesized that elevated cisternal 5-HIAA was associated with reduced neurotrophic effects, conceivably due to excessive negative feedback at somatodendritic 5-HT1A autoreceptors. A putatively decreased serotonin neurotransmission would be reflected by reductions in hippocampal volume and white matter (WM) fractional anisotropy (FA).


Methods: When infants were 2–6 months of age, bonnet macaque mothers were exposed to VFD. We employed cisternal CSF taps to measure monoamine metabolites in VFD (N = 22) and non-VFD (N = 14) offspring (mean age = 2.61 years). Metabolites were correlated with hippocampal volume obtained by MRI and WM FA by diffusion tensor imaging in young adulthood in 17 males [10 VFD (mean age = 4.57 years)].


Results: VFD subjects exhibited increased CSF 5-HIAA compared to non-VFD controls. An inverse correlation between right hippocampal volume and 5-HIAA was noted in VFD- but not controls. CSF HVA and MHPG correlated inversely with hippocampal volume only in VFD. CSF 5-HIAA correlated inversely with FA of the WM tracts of the anterior limb of the internal capsule (ALIC) only in VFD.


Conclusions: Elevated cisternal 5-HIAA in VFD may reflect increased dorsal raphe serotonin, potentially inducing excessive autoreceptor activation, inducing a putative serotonin deficit in terminal fields. Resultant reductions in neurotrophic activity are reflected by smaller right hippocampal volume. Convergent evidence of reduced neurotrophic activity in association with high CSF 5-HIAA in VFD was reflected by reduced FA of the ALIC.

Full Citation: 
Coplan JD, Fulton SL, Reiner W, Jackowski A, Panthangi V, Perera TD, Gorman JM, Huang Y, Tang CY, Hof PR, Kaffman A, Dwork AJ, Mathew SJ, Kaufman J and Mann JJ (2014, Dec 24). Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function in mood and anxiety disorders. Front. Behav. Neurosci. 8:440. doi: 10.3389/fnbeh.2014.00440

* * * * *

A neurobiological hypothesis of treatment-resistant depression – mechanisms for selective serotonin reuptake inhibitor non-efficacy


Jeremy D. Coplan1*, Srinath Gopinath1, Chadi G. Abdallah2,3 and Benjamin R. Berry4

  • 1Division of Neuropsychopharmacology, Department of Psychiatry and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY, USA
  • 2Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
  • 3Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA
  • 4State University of New York Downstate College of Medicine, Brooklyn, NY, USA
First-line treatment of major depression includes administration of a selective serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates following two trials of an SSRI are <50%. The authors examine the putative biological substrates underlying “treatment resistant depression (TRD)” with the goal of elucidating novel rationales to treat TRD. We look at relevant articles from the preclinical and clinical literature combined with clinical exposure to TRD patients. A major focus was to outline pathophysiological mechanisms whereby the serotonin system becomes impervious to the desired enhancement of serotonin neurotransmission by SSRIs. A complementary focus was to dissect neurotransmitter systems, which serve to inhibit the dorsal raphe. We propose, based on a body of translational studies, TRD may not represent a simple serotonin deficit state but rather an excess of midbrain peri-raphe serotonin and subsequent deficit at key fronto-limbic projection sites, with ultimate compromise in serotonin-mediated neuroplasticity. Glutamate, serotonin, noradrenaline, and histamine are activated by stress and exert an inhibitory effect on serotonin outflow, in part by “flooding” 5-HT1A autoreceptors by serotonin itself. Certain factors putatively exacerbate this scenario – presence of the short arm of the serotonin transporter gene, early-life adversity and comorbid bipolar disorder – each of which has been associated with SSRI-treatment resistance. By utilizing an incremental approach, we provide a system for treating the TRD patient based on a strategy of rescuing serotonin neurotransmission from a state of SSRI-induced dorsal raphe stasis. This calls for “stacked” interventions, with an SSRI base, targeting, if necessary, the glutamatergic, serotonergic, noradrenergic, and histaminergic systems, thereby successively eliminating the inhibitory effects each are capable of exerting on serotonin neurons. Future studies are recommended to test this biologically based approach for treatment of TRD.

Full Citation: 
Coplan JD, Gopinath S, Abdallah CG and Berry BR. (2014, May 20). A neurobiological hypothesis of treatment-resistant depression – mechanisms for selective serotonin reuptake inhibitor non-efficacy. Front. Behav. Neurosci. 8:189. doi: 10.3389/fnbeh.2014.00189

Wednesday, March 04, 2015

Psychosocial Stress, Inflammation, and Adhesion Molecules

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I have been re-reading a book by Joseph LeDoux (NYU), Synaptic Self: How Our Brains Become Who We Are (2002), in which he argues that synapses in the brain are the foundation of personality, the basis of our sense of self:

My notion of personality is pretty simple: it‟s that your “self,” the essence of who you are, reflects patterns of interconnectivity between neurons in your brain. Connections between neurons, known as synapses, are the main channels of information flow and storage in the brain. Most of what the brain does is accomplished by synaptic transmission between neurons, and by calling upon the information encoded by past transmission across synapses. (p. 3-4)

This is relevant to some of the work I have been doing for Dr. Cress at the University of Arizona Cancer Center. Dr. Cress has been working for many years on the function of integrins in cancer metastasis, specifically in prostate cancer.

Here is how integrins are defined at Wikipedia, which is as precise as any you will find.
Integrins are transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions. When triggered, integrins in turn trigger chemical pathways to the interior (signal transduction), such as the chemical composition and mechanical status of the ECM, which results in a response (activation of transcription) such as regulation of the cell cycle, cell shape, and/or motility; or new receptors being added to the cell membrane. This allows rapid and flexible responses to events at the cell surface, for example to signal platelets to initiate an interaction with coagulation factors.

There are several types of integrins, and a cell may have several types on its surface. Integrins are found in all metazoa.[3]

Integrins work alongside other receptors such as cadherins, the immunoglobulin superfamily cell adhesion molecules, selectins and syndecans to mediate cell–cell and cell–matrix interaction. Ligands for integrins include fibronectin, vitronectin, collagen, and laminin.
Integrins are heterdimic adhesion receptors, meaning they have two different parts, the α (alpha) and β (beta) subunits. There are at least 18 α and eight β subunits are known in humans and other vertebrates (Takada, Ye, & Simon, 2007).

Dr. Cress has been work with the A6B4 integrin (alpha 6 beta 4) and its role in metastatic prostate cancer. A6 is one of three laminin-binding molecules in humans (the others are A3 and A7), although other researchers suggest there are five laminin-binding integrins, A1, A2, A3, A6, A7 (Alberts, Johnson, & Lewis; 2007; Molecular Biology of the Cell. 5th edition). This graphic explains the functions of the different integrins and their combinations.


Integrins are also expressed in the brain, especially in synapses and in the lamination of axons, which allows information to more quickly and efficiently through the brain (and through neural cells throughout the body). Schwann cells in peripheral nerves interact with axons and extracellular matrix (ECM) as part of their work in ensheathing and myelinating axons and they express B4 (beta 4 integrin) [Feltri, et al, 1994], and specifically A6B4. 

In digging around for additional information on synapses and brain function, I found a related article by LeDoux - this is the abstract (crucial section is in bold):

STRUCTURAL PLASTICITY AND MEMORY
Raphael Lamprecht and Joseph LeDoux

Much evidence indicates that, after learning, memories are created by alterations in glutamate-dependent excitatory synaptic transmission. These modifications are then actively stabilized, over hours or days, by structural changes at postsynaptic sites on dendritic spines. The mechanisms of this structural plasticity are poorly understood, but recent findings are beginning to provide clues. The changes in synaptic transmission are initiated by elevations in intracellular calcium and consequent activation of second messenger signalling pathways in the postsynaptic neuron. These pathways involve intracellular kinases and GTPases, downstream from glutamate receptors, that regulate and coordinate both cytoskeletal and adhesion remodelling, leading to new synaptic connections. Rapid changes in cytoskeletal and adhesion molecules after learning contribute to short-term plasticity and memory, whereas later changes, which depend on de novo protein synthesis as well as the early modifications, seem to be required for the persistence of long-term memory.
Source: Nature Reviews Neuroscience; January 2004; 5(1):45-54. doi:10.1038/nrn1301 
Rho GTPaseas mediate extracellular stimulation-induced actin cytoskeleton rearrangements. Stimulation of the postsynaptic neuron leads to actin-dependent morphological changes mediated by Rho GTPases105–108. 1) Activation of adhesion molecules, such as integrin or cadherin, which have been shown to be involved in synaptic plasticity, regulates Rho GTPase inactivation by RhoGAPs. 2) Calcium influx through membrane channels can induce activation of tyrosine kinases (TKs), such as the cell adhesion kinase-β/proline-rich tyrosine kinase 2 (CAKβ/Pyk2), that in turn activate Src. The later modulates p190 RhoGAP activity and thereby controls Rho GTPase inactivation. 3) On the other hand, Rho GTPase activators, RhoGEFs, are also regulated by extracellular stimulation. Ephrin A activates, through the receptor tyrosine kinase EphA, a Rho GEF called ephexin. EphA has been implicated in memory formation133. 4) Rho GTPase controls actin polymerization through downstream effectors such as Rho-associated kinase (ROCK). ROCK activates LIM-domain-containing protein kinase (LIMK), which in turn inhibits the actin depolymerizing factor cofilin. This event can contribute to actin polymerization. ROCK, LIMK and cofilin have been shown to be involved in synaptic plasticity. 5) Cdc42 and Rac, other members of the Rho GTPase family, induce actin polymerization by regulating downstream effectors. GAP, GTPase-activating protein; GEF, guanine nucleotide exchange factor; N-WASP, neuronal Wiskott-Aldrich syndrome; SCAR, suppressor of cAR.
The text above is the caption for the image. Here is another quote from near the end of the paper, which is minimal and could be the topic of an entire paper:
Adhesion molecules and synaptic plasticity 

The formation of new synaptic contacts is a dynamic process that involves ongoing morphological alterations and modulation of adhesion between the pre- and postsynaptic neurons [115,116]. These processes require coordinated activity between molecules that regulate cytoskeletal rearrangements and morphology, and those that control adhesion between the pre- and postsynaptic membranes.Adhesion molecules, mostly integrins, cadherins, neurexin and the immunoglobulin superfamily, are membrane-bound molecules that have hetero- or homophilic interactions with proteins in the extracellular matrix and synaptic membranes to control the adhesion between the pre- and postsynaptic membranes. Adhesion molecules, which also have an intracellular component, can initiate signalling pathways that couple the dynamics of extracellular connectivity with intracellular events that control morphology. For example, cadherin regulates dendritic spine morphogenesis and function. Blockade of cadherin function leads to elongation of the spine, bifurcation of its head structure and alterations in the distribution of postsynaptic proteins [117]. Moreover, neuronal activity induces the movement of β-catenin (which mediates the interaction of cadherin with the actin cytoskeleton) from dendritic shafts into spines to become associated with cadherin and to influence synaptic size and strength [118]. Adhesion molecules such as cadherin also associate with molecules that regulate cytoskeletal rearrangements, such as proteins that control the Rho GTPase pathway [119].

Adhesion molecules could therefore contribute to the morphological alteration and stabilization of connectivity between neurons, a process that is hypothesized to underlie memory consolidation. Consistent with this hypothesis is the role of adhesion molecules in the formation and stabilization of LTP and LTM. Integrin-mediated adhesion helps to stabilize early-phase LTP (E-LTP) into late-phase LTP (L-LTP). For example, inhibition of integrin with a peptide that contains the integrin recognition sequence 10 min before, immediately after and 10 min after LTP induction caused a gradual decay of synaptic strength over 40 min [120]. The peptide had no effect when applied 25 min after LTP initiation, indicating that integrin has a role in stabilization of synaptic connectivity. Furthermore, N-cadherin is synthesized and internalized to new assembled synapses during the induction of L-LTP, and blocking N-cadherin adhesion prevents the induction of L-LTP but not E-LTP [121]. This event depends on glutamate receptor activity. In chicks, memory is impaired 24 h after a visual categorization task when antibodies against the cell adhesion molecule L1 are injected before, 5.5 h or 15–18 h after training (but not later) [122]. In addition, intraventricular injection of antibodies against neural cell adhesion molecule (NCAM) in rats 6–8 h after passive avoidance training, but not later, impaired retention of the avoidance response [123]. These observations indicate that adhesion molecules are essential for memory consolidation during a period of hours after acquisition.


The level and distribution of adhesion molecules is also correlated with synaptic plasticity and learning. In Aplysia, repeated application of 5-hydroxytryptamine (serotonin; 5-HT), which leads to long-term facilitation of the sensory–motor connection, induces the internalization of the adhesion molecule apCAM (Aplysia cell adhesion molecule) [43]. This could destabilize the interaction between sensory neurons, permitting the growth of new sensory axons.ApCAM could be redistributed to the area where new synapses are formed. In rats, N-cadherin is induced in the piriform cortex and hypothalamus 2 h after fear conditioning [124]. N-cadherin was not induced in control animals that were presented with the conditioned stimulus and unconditioned stimulus in a non-associative manner.


On the whole, these observations indicate that adhesion molecules have a central role in mediating neuronal connectivity and morphogenesis, and in the progressive stabilization of synaptic connectivity that leads to memory consolidation. (LeDoux, 2004, pages 50-51)

I did some more digging and found that A3, A5, A8, and B1 (McGeachie, Cingolani, & Godaare, 2011) are all expressed in synaptic formation and function and in the growth and activity of dendrites. If the alpha versions of the integrins are not functioning properly, learning and memory are inhibited, but there are differences for each of the alpha integrins and for the beta integrin:
Interestingly, behavioural tests revealed specific deficits in hippocampal-dependent working memory, while spatial memory was unaffected. Although ITGβ1 is likely to be the major subunit for ITGα3, ITGα5 and ITGα8 in the hippocampus (Hynes, 2002), ITGα3/+;ITGα5/+;ITGα8/+ mice showed behavioural deficits (see above) that are different from those of ITGβ1 conditional knockout mice. Such divergent results may reflect the differences arising from global reduction in ITGα3, ITGα5 and ITGα8 versus a more specific ablation of ITGβ1 mainly in CA1 pyramidal neurons.
[In the quote above, ITGα3, and so on, is used to represent integrin (ITG) alpha 3.] 

Inflammation from Psychosocial Stress

We know that psychosocial stress causes inflammation. University of Arizona researcher/professor Charles Raison (2006) found that depressed patients have higher levels of proinflammatory cytokines, acute phase proteins, chemokines, and cellular adhesion molecules (an important finding for my thesis). It has also been shown that therapeutic administration of the cytokine interferon-α (a cancer treatment drug that inhibits tumor cell growth) leads to depression in up to 50% of patients (Bonaccorso, et al, 2002).

Stress appears to down-regulate immunity through at least three mechanisms:
(A) Stress hormones are influenced by negative events and negative emotions: catecholamines (adrenaline and noradrenaline), adrenocorticotropic hormone (ACTH), cortisol, growth hormone, and prolactin, as examples

(B) Immune modulation by these hormones proceeds through two pathways
1. Directly, through binding of the hormone to its cognate receptor at the surface of a cell 
2. Indirectly — for example, by inducing dysregulation of the production of cytokines, such as interferon-γ (IFN-γ), interleukin-1 (IL-1),IL-2,IL-6 and tumour-necrosis factor (TNF)
Cytokines such as IFN-γ have many functions and affect different target cells. Therefore, there are secondary effects of many stress hormones on the immune response

(C) Communication between the CNS and the immune system is bidirectional - examples: 
1. IL-1 influences the production of corticotropin-releasing hormone (CRH) by the hypothalamus. In turn, CRH can affect the HPA axis and thereby trigger increases in stress hormone levels, which results in dysregulation of immune function 
2. Lymphocytes can synthesize hormones such as ACTH, prolactin and growth hormone
Glaser, R., & Kiecolt-Glaser, J. K. (2005). Stress-induced immune dysfunction: implications for health. Nature Reviews Immunology, 5(3), 243-251.

Here is the abstract (edited for relevance) from an excellent review article: Psychosocial stress and inflammation in cancer by Powell, Tarr, and Sheridan (2013) that provides some useful information about how stress (i.e., trauma) can compromise the immune system. [Bold area is my emphasis.]
Stress-induced immune dysregulation results in significant health consequences for immune related disorders including viral infections, chronic autoimmune disease, and tumor growth and metastasis.  Both human and animal studies have shown the sympathetic and neuroendocrine responses to psychosocial stress significantly impacts cancer, in part, through regulation of inflammatory mediators. Psychosocial stressors stimulate neuroendocrine, sympathetic, and immune responses that result in the activation of the hypothalamic–pituitary–adrenal (HPA)-axis, sympathetic nervous system (SNS), and the subsequent regulation of inflammatory responses by immune cells. Social disruption (SDR) stress, a murine model of psychosocial stress and repeated social defeat, provides a novel and powerful tool to probe the mechanisms leading to stress-induced alterations in inflammation, tumor growth, progression, and metastasis.
The following is from the first section of the same paper and it provides an overview of the chemical pathways involved in stress-induced inflammation.
[S]tudies using a mouse model of repeated social defeat, termed social disruption (SDR) stress, have shown that stress alone can trigger the generation, egress, and trafficking of immature, inflammatory myeloid derived-cells that are glucocorticoid (GC) insensitive (Curry et al., 2010, Engler et al., 2004a and Engler et al., 2005). In addition, these GC insensitive cells produce high levels of IL-6 and other inflammatory cytokines and chemokines (Powell et al., 2009, Stark et al., 2002 and Wohleb et al., 2011). As a consequence, these stress-induced changes at the cellular level translate to significant immune (enhanced inflammatory responses and immunity to microbial, viral, and allergen challenge) and behavioral (prolonged anxiety-like behavior) changes (Bailey et al., 2007, Bailey et al., 2009b, Bailey et al., 2009a, Dong-Newsom et al., 2010, Kinsey et al., 2007, Mays et al., 2010, Mays et al., 2012, Powell et al., 2011 and Wohleb et al., 2011). Indicative of the important role of the SNS in stress-induced immune alteration, these changes are reversed by the blockade of sympathetic signaling prior to stressor exposure (Wohleb et al., 2011).
The stress response in vertebrates stems from internal or external stimuli that trigger the “fight or flight” and "defeat/withdrawal" responses expressed in sympathetic nervous system (SNS) and the hypothalamic–pituitary–adrenal (HPA)-axis activation. Years of research has shown that specific central nervous system (CNS) pathways function as translators of social stimuli into peripheral biological signals that regulate inflammatory responses.
For instance, stress activates neuroendocrine and autonomic pathways like the HPA axis, and the SNS resulting in the release of GC, catecholamines, and pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α. The release of these sympathetic, neuroendocrine, and immune factors has a profound influence on immunity, behavior, and physiology in both humans and rodents and triggers peripheral biological responses that, in turn, signal back to the CNS to complete a bi-directional communication circuit. This is evident in models of repeated social defeat, like SDR, that enhance immune responses to microbial, viral, and allergic challenges and promote and prolong anxiety-like behavior in rodents (Kinsey et al., 2007, Bailey et al., 2009a, Bailey et al., 2009b and Mays et al., 2010). Social disruption stress-induced prolonged anxiety-like behavior coincides with a unique pattern of c-Fos activation in brain regions associated with fear and threat appraisal. For example, repeated social defeat, termed social disruption (SDR) causes increased c-Fos activation in the prefrontal cortex, amygdala, hippocampus, paraventricular nucleus, bed nucleus of the stria terminalis and the lateral septum (Wohleb et al., 2011). [Powell, Tarr, and Sheridan, 2013, p. 3]
When the HPA and SNS circuitry are activated, the release of neurotransmitters and stress hormones generates compensatory physiologic changes that impact behavior and the function of the immune system. In humans, chronic or repeated exposure to stress appears to lead to increases in the expression of inflammatory biomarkers, worsened disease states, and affective/emotional disorders (Glaser and Kiecolt-Glaser, 2005; Gouin et al., 2012).

In several studies, stressed individuals exhibit reduced anti-inflammatory glucocorticoid regulation and increased inflammatory nuclear factor (NF)-κB signaling (Miller et al., 2008). In these situations, psychosocial stress represents a challenge to homeostasis that manifests as physiological alterations in the body (Glaser and Kiecolt-Glaser, 2005).

This may be something to look at in terms of how trauma impacts the brain and body, a microbiological model of traumatic stress, inflammation, and the alteration of adhesion molecules, all of which leads to impaired learning and impaired memory.

As of now, there are no known interventions at the cellular level for altering integrin function. However, the are many ways to control and eliminate inflammation. Among the most well-researched (I could provide citations for these, but it's late, so I might add them later):
1) Curcumin/turmeric
2) Resveratrol
3) Exercise
4) Stress-reduction techniques, such as meditation
5) Avoiding smoking, drinking, and processed foods
We have some control over how our bodies manage and adapt to stress. We are not merely victims of our biology.