Saturday, April 27, 2013

Psychopaths Are Not Neurally Equipped to Have Concern for Others

Gee, ya think?

The study was conducted by Jean Decety, the Irving B. Harris Professor in Psychology and Psychiatry at UChicago. Decety: "This is the first time that neural processes associated with empathic processing have been directly examined in individuals with psychopathy, especially in response to the perception of other people in pain or distress."

Psychopaths are not neurally equipped to have concern for others, study shows

April 24, 2013

Prisoners who are psychopaths lack the basic neurophysiological "hardwiring" that enables them to care for others, according to a new study by neuroscientists at the University of Chicago and the University of New Mexico.

"A marked lack of empathy is a hallmark characteristic of individuals with psychopathy," said the lead author of the study, Jean Decety, the Irving B. Harris Professor in Psychology and Psychiatry at UChicago. Psychopathy affects approximately 1 percent of the United States general population and 20 percent to 30 percent of the male and female U.S. prison population. Relative to non-psychopathic criminals, psychopaths are responsible for a disproportionate amount of repetitive crime and violence in society.

"This is the first time that neural processes associated with empathic processing have been directly examined in individuals with psychopathy, especially in response to the perception of other people in pain or distress," he added.

The results of the study, which could help clinical psychologists design better treatment programs for psychopaths, are published in the article, "Brain Responses to Empathy-Eliciting Scenarios Involving Pain in Incarcerated Individuals with Psychopathy," which appears online April 24 in the journal JAMA Psychiatry.

Joining Decety in the study were Laurie Skelly, a graduate student at UChicago; and Kent Kiehl, professor of psychology at the University of New Mexico.

For the study, the research team tested 80 prisoners between ages 18 and 50 at a correctional facility. The men volunteered for the test and were tested for levels of psychopathy using standard measures.

They were then studied with functional MRI technology, to determine their responses to a series of scenarios depicting people being intentionally hurt. They were also tested on their responses to seeing short videos of facial expressions showing pain.

The participants in the high psychopathy group exhibited significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, amygdala and periaqueductal gray parts of the brain, but more activity in the striatum and the insula when compared to control participants, the study found.

The high response in the insula in psychopaths was an unexpected finding, as this region is critically involved in emotion and somatic resonance. Conversely, the diminished response in the ventromedial prefrontal cortex and amygdala is consistent with the affective neuroscience literature on psychopathy. This latter region is important for monitoring ongoing behavior, estimating consequences and incorporating emotional learning into moral decision-making, and plays a fundamental role in empathic concern and valuing the well-being of others.

"The neural response to distress of others such as pain is thought to reflect an aversive response in the observer that may act as a trigger to inhibit aggression or prompt motivation to help," the authors write in the paper.

"Hence, examining the neural response of individuals with psychopathy as they view others being harmed or expressing pain is an effective probe into the neural processes underlying affective and empathy deficits in psychopathy," the authors wrote.

Decety is one of the world's leading experts on the biological underpinnings of empathy. His work also focuses on the development of empathy and morality in children.

The study with prisoners was supported with a $1.6 million grant from the National Institute of Mental Health.

Journal reference: JAMA Psychiatry
Provided by University of Chicago

Jesse Singal - Daniel Kahneman’s Gripe With Behavioral Economics

From The Daily Beast, this is an interesting interview on his "issues" with the field of behavioral economics, a field which some credit him with creating.

Daniel Kahneman’s Gripe With Behavioral Economics

Nobel-winning psychologist Daniel Kahneman explains his problem with people using the term ‘behavioral economics.’

Apr 26, 2013

If you’re looking to better understand your own brain and only have time to read one book on the subject, it should be Daniel Kahneman’s Thinking, Fast and Slow, now out in paperback. Kahneman, a psychologist at Princeton University who won the 2002 Nobel Prize for economics for work that he and longtime collaborator Amos Tversky did on the psychology of decision making, gives a detailed, comprehensive account of how our cognitive processes are divided into fast (“System 1”) and slow (“System 2”) thinking. System 1 handles basic tasks and calculations like walking, breathing, and determining the value of 1 + 1, while System 2 takes on more complicated, abstract decision making and calculations like 435 x 23. Many of our mistakes, Kahneman writes, come when exhaustion or other factors cause System 1 to do jobs better suited for System 2.

Thinking, Fast and Slow’ by Daniel Kahneman. 512 pp. FSG. $16. (AP)

In a recent email interview, Kahneman explains the dangers of overconfidence, why economists are still at the top of the policy-making pecking order, and his good-natured gripe with the term “behavioral economics.”

It seems like overconfidence is one of the big targets of Thinking, Fast and Slow. Unfortunately, there’s some evidence that people are more drawn to those who exhibit this tendency, even when it isn’t warranted (such as political prognosticators). How do we get around our ingrained tendencies to be attracted to those who loudly proclaim easy answers?

This is most difficult where it matters the most, in running a democracy. People like leaders who look like they are dominant, optimistic, friendly to their friends, and quick on the trigger when it comes to enemies. They like boldness and despise the appearance of timidity and protracted doubt. Here, the hope for the selection of qualified leaders is in serious and critical media, but the incentives of popular media favor mirroring the preferences of the public, however misguided.

Prospects are quite a bit better for the selection of good leaders in organizations. In business enterprises as well as in politics, the more assertive and confident individuals have a big advantage, especially if they are also lucky and achieve a few early successes. But organizations are better placed to evaluate people by substantive achievements and by their contributions to the conversation. They can apply slow thinking to the selection of leaders, and they should.

Do you see any resistance to the ideas in Thinking, Fast and Slow from people who don’t want to acknowledge how error-prone the human brain can be under certain circumstances? 
Amos Tversky and I encountered this kind of resistance to our early work, which was focused mostly on errors of judgment, rather than on intelligent performance. Some people chose to infer that we believed humans to be feeble-minded, which we never did. Thinking, Fast and Slow is explicit in offering a view of the mind that deals with marvels as well as flaws, and it has largely escaped the criticism that it is biased against human nature. However, I have encountered some people, especially in the field of finance, who can easily think of individuals (often themselves, sometimes Warren Buffett) who understand the world with far more precision than my book suggests anyone can.

What has it been like winning the Nobel Prize and seeing your work explode in popularity without Amos Tversky around to share these experiences with you?

The work was already quite well known before Amos’s death, and he knew before he died that we had been nominated for the Nobel and were quite likely to get it eventually. For him, the Nobel was one of many things that he was going to miss by dying at 59, and certainly not the most important. As for me, I never forget that the recognition I get is for work that was done by a successful team of which I was lucky to be a member.

It’s a complicated question, but what is the simplest, most straightforward advice you’d give to someone who wants to make sure their System 2 isn’t ceding certain important decisions and calculations to System 1?

Not really a complicated question because the answers are not surprising. Slow down, sleep on it, and ask your most brutal and least empathetic close friends for their advice. Friends are sometimes a big help when they share your feelings. In the context of decisions, the friends who will serve you best are those who understand your feelings but are not overly impressed by them. For example, one important source of bad decisions is loss aversion, by which we put far more weight on what we may lose than on what we may gain. Advisors are likely to give us advice in which gains and losses are treated more neutrally—they are more likely to adopt a broad and long-term view of our problem, less likely than the affected individual to be swayed by the fears and hopes of the moment.

You note in the foreword to the recently released The Behavioral Foundations of Public Policy that economists have a “monopoly” on policy making, that. “Like it or not, it is a fact of life that economics is the only social science that is generally recognized as relevant and useful by policy makers.” Why is that? 
Policy makers, like most people, normally feel that they already know all the psychology and all the sociology they are likely to need for their decisions. I don’t think they are right, but that’s the way it is. On the other hand, people who have not studied economics are fully aware of their ignorance. The use of mathematics adds a touch of magic to economics. Indeed it makes perfect sense for economists to be the interpreters of policy-relevant research, because they understand and are trained to use big data. This, and the fact that policies always involve tradeoffs and almost always involve money, explains the dominant role of economics in policy.

Something else has happened in recent years that is amusing, but also frustrating for psychologists. When it comes to policy making, applications of social or cognitive psychology are now routinely labeled behavioral economics. The “culprits” in the appropriation of my discipline are two of my best friends, Richard Thaler and Cass Sunstein. Their joint masterpiece Nudge is rich in policy recommendations that apply psychology to problems—sometimes common-sense psychology, sometimes the scientific kind. Indeed, there is far more psychology than economics in Nudge. But because one of the authors ofNudge is the guru of behavioral economics, the book immediately became the public definition of behavioral economics. The consequence is that psychologists applying their field to policy issues are now seen as doing behavioral economics. As a result, they are almost forced to accept the label of behavioral economists, even if they are as innocent of economic knowledge as I am. Furthermore, these psychologists are rewarded by greater attention to their ideas, because they benefit from the higher credibility that comes to credentialed economists.

Obviously you (and Eldar Shafir, and other researchers) are hoping to change this, to have psychology better represented at the policy-making table. Where do you think Thinking, Fast and Slow has fit into this effort, and what’s next in the ongoing attempt to weave psychological findings more tightly into public policy?

The intrepid readers who get close to the end of my long tome will find an enthusiastic endorsement of the policy applications that have come under the label of behavioral economics. I am very optimistic about the future of that work, which is characterized by achieving medium-sized gains by nano-sized investments. But I hope that the work will eventually be recognized for what it is and relabeled. In the U.K., for example, there is a unit doing that work at 10 Downing Street. Its informal name is “the Nudge Unit” and its formal name is the “Behavioural Insights Team.” It is headed by a psychologist. The value of proper labeling is that good psychologists are more likely to be drawn to participate in efforts that explicitly recognize their discipline.

What’s so powerful about the rational actor model? Do you think economists will ever willingly give up those parts of it which should be discarded?

Think of the kind of market that Adam Smith described. You can get a lot of insight into how just the right amount of bread gets to London in the morning by assuming that the baker and the other participants in the market pursue their own interests in a sensible manner. The rational-agent model takes this idea to its logical extreme. If you want to predict the behavior of a market, you are best off assuming individual agents who act in a way that is predictable and fairly simple—for example by assuming that the participants are similarly motivated and exploit all their opportunities. I am not an economist, but I find it hard to imagine that they will ever give up the use of schematic individual agents, even if they endow these agents with a little more realistic psychology. And I see no reason why they should.

The rational agent model has more questionable consequences in the domain of policy because the assumption that individuals are rational in the pursuit of their interests has an ideological coloring and policy implications that many would view as unfortunate. If individuals are rational, there is no need to protect them against their own choices. At the extreme, no need for Social Security or for laws that compel motorcycle riders to wear helmets. It is not an accident that the department of economics at Chicago University, one of the most illustrious in the world, is known both for its adherence to a strict version of the rational actor model and for very conservative politics.

It seems as though there are many areas in which economists and psychologists are vying for the same public-policy space. How do you get around the fact that economists can produce elegant models, nifty graphs, and the like (even when the underlying ideas aren’t sturdy), but psychology research isn’t always quite so easy to present to policy makers in a shiny, impressive-looking way? 
You should not play down psychologists’ ability to turn out nifty Power Point slides. More seriously, I see much more collaboration than competition between psychologists and economists in the domain of policy, and my only quibble is with the label. I would like them all, when they collaborate, to call themselves behavioral scientists. The synergy is evident in policy books such as Cass Sunstein’s Simpler and the forthcoming Scarcity: Why Having Too Little Means So Much, by Sendhil Mullainathan and Eldar Shafir which deals with both the economics and the psychology of poverty.

Walk the Talk Show with Waylon Lewis: Joan Halifax Roshi

From Elephant Journal - Waylon Lewis interviews Joan Halifax Roshi, one of the most popular and (imo) compassionate (Zen) Buddhist teachers in the West. Part of the discussion involves the new Google+ Community on Engaged Buddhism started by Roshi and the Upaya Zen Center.

Recently Roshi Joan and Upaya Zen Center launched a Google+ Community on Engaged Buddhism.Please visit & join this growing and active community.
Engaged Buddhism

Walk the Talk Show: Joan Halifax Roshi: How to Balance Inner Work & Outer Social Activism

Walk the Talk Show with Waylon Lewis: Joan Halifax Roshi.
Apologies for the many sound problems . . . I’d advise just watching and listening while it’s synched, then just listening. Apologies, and deep thanks to Halifax Roshi! ~ ed.
Waylon sits with leading Zen Buddhist teacher Joan Halifax. They talk re: how to balance inner work & outer social activism.

She’s awesome.

Friday, April 26, 2013

How Your Unconscious Mind Rules Your Behaviour: Leonard Mlodinow at TEDxReset 2013

Leonard Mlodinow is the author of Subliminal: How Your Unconscious Mind Rules Your Behavior - one of my selections for best books from 2012. Here is an outline of the book from Amazon:
Over the past two decades of neurological research, it has become increasingly clear that the way we experience the world--our perception, behavior, memory, and social judgment--is largely driven by the mind's subliminal processes and not by the conscious ones, as we have long believed. As in the bestselling The Drunkard’s Walk: How Randomness Rules Our Lives, Leonard Mlodinow employs his signature concise, accessible explanations of the most obscure scientific subjects to unravel the complexities of the subliminal mind. In the process he shows the many ways it influences how we misperceive our relationships with family, friends, and business associates; how we misunderstand the reasons for our investment decisions; and how we misremember important events--along the way, changing our view of ourselves and the world around us.
Here is his recent TEDx talk from TEDxReset.

How Your Unconscious Mind Rules Your Behaviour: Leonard Mlodinow at TEDxReset 2013

Published on Apr 25, 2013

As a child, Leonard was interested in both mathematics, chemistry and organic chemistry. His interest turned to physics during a semester he took off from college to spend on a kibbutz in Israel, during which he had little to do at night beside reading The Feynman Lectures on Physics. While a doctoral student at the University of California, Berkeley and on the faculty at Caltech, he co-developed a new type of perturbation theory for eigenvalue problems in quantum mechanics Later, he did pioneering work on the quantum theory of dielectric media. Between 2008 and 2010, Mlodinow worked on a book with Stephen Hawking, entitled The Grand Design. Apart from his research and books on popular science, he has been a screenwriter for television series, including Star Trek: The Next Generation and MacGyver.

Toni Bernhard, J.D. - Tapping into Self-Compassion to Help Ease Everyday Suffering

This post from Toni Bernhard, J.D. on her Turning Straw Into Gold blog at Psychology Today offers some nice quotations on how to treat ourselves with compassion in the face of our losses.

Tapping into Self-Compassion to Help Ease Everyday Suffering

There is never a good reason not to treat yourself with kindness and compassion.

Published on April 21, 2013 by Toni Bernhard, J.D. in Turning Straw Into Gold

Young Woman Braiding Her Hair

When I posted my last article, “8 Things I Miss as a Result of Chronic Pain and Illness,” I wasn’t planning to write a follow-up. But it became clear within hours of posting it that the piece had struck a chord with many readers. People began sharing the many losses they were feeling as the result of their health limitations. Others said they cried as they read my list because it tapped into their own feelings of deep loss.

By the end of the day, I began to feel that the piece had left some people feeling worse than they had before reading it, even though my intent was to acknowledge how things are for me in a way that I thought might help all of us accept our life as it is.

My initial idea for a follow-up was to share other people’s comments about what they miss most due to their health limitations. But my heart dictated otherwise. It said: “It’s enough for us to bear our own losses; what we need is help learning to treat ourselves with compassion over those losses.”

And so, I’ve carefully gathered fifteen quotations that I thought would help with this task. Some are from spiritual teachers; some are from philosophers and other writers; others are from people who have various self-compassion projects in the works (you can Google the names of any people you’d like to know more about). I’ve chosen several portraits by Pierre-Auguste Renoir to accompany the piece.

I hope some of these quotations will enter your heart and perhaps (as they have for me) even find themselves jotted down on scraps of paper to keep by your side.

Madame Renoir

“You are taught that there is something wrong with you and that you are imperfect. But there isn’t and you’re not.” —Cheri Huber

"Having compassion starts and ends with having compassion for all those unwanted parts of ourselves. The healing comes from letting there be room for all of this to happen: room for grief, for relief, for misery, for joy." —Pema Chödrön

“To be yourself in a world that is constantly trying to make you something else is the greatest accomplishment.” —Ralph Waldo Emerson

"Often we treat certain aspects of ourselves as junk, having no value. We try to throw parts of ourselves in the garbage. But a human being is an ecosystem, and everything in that system is of value to the whole." —Stephen Schwartz

"If your compassion does not include yourself, it is incomplete." —Jack Kornfield

"Self-compassion is approaching ourselves, our inner experience with spaciousness, with the quality of allowing, which has a quality of gentleness. Instead of our usual tendency to want to get over something, to fix it, to make it go away, the path of compassion is totally different. Compassion allows." —Robert Gonzales

“Self-acceptance is my refusal to be in an adversarial relationship to myself.” —Nathaniel Brand

Paul Meunier

“One's dignity may be assaulted, vandalized and cruelly mocked, but it can never be taken away unless it is surrendered.” —Michael J. Fox

“Be faithful to that which exists within yourself.” —André Gide

“When the heart acknowledges how much pain there is in the mind, it turns like a mother toward a frightened child.” —Stephen Levine

“You don’t want to beat yourself up for beating yourself up in the vain hope that it will somehow make you stop beating yourself up. Just as hate can’t conquer hate—but only strengthens and reinforces it—self-judgment can’t stop self-judgment. The best way to counteract self-criticism, therefore, is to understand it, have compassion for it, and then replace it with a kinder response.” —Kristin Neff

“The privilege of a lifetime is being who you are.” —Joseph Campbell

Jeanne Samary 
“Simplicity, patience, and compassion are your greatest treasures. Simple in actions and thoughts, you return to the source of being. Patient with both friends and enemies, you accord with the way things are. Compassionate toward yourself, you reconcile all beings in the world.” —Lao Tzu

“It’s not your job to like me. It’s mine.” —Byron Katie

Because this piece is made up largely of quotations, I’ll take the liberty of ending it by quoting myself from my upcoming book:
“We can’t always control the world outside of us, but we can learn to control our inner world, by which I mean how we treat ourselves and how we regard ourselves. In my view, there’s never a good reason not to treat ourselves with the same kindness and compassion that we treat those who are most beloved to us, and there’s never a good reason to regard ourselves as unworthy.”
© 2013 Toni Bernhard

I'm the author of the Nautilus Gold Medal winner How to Be Sick: A Buddhist-Inspired Guide for the Chronically Ill and their Caregivers.

My most recent book is titled How to Wake Up: A Buddhist-Inspired Guide to Navigating Joy and Sorrow (September 10, 2013 release date).

Please join me on Facebook, Twitter, Pinterest. You can also subscribe to my blog—see the choices above my picture on this page.

World Thinkers 2013 - Intellectuals Who Shape Our Thinking

This is clearly a British list, or at least the people who assembled it seem to be - it was commissioned and published by Prospect Magazine, from the UK. The placing of Richard Dawkins as the top thinker is a bit more than slightly disconcerting. Dawkins is a close-minded reductionist ideologue, and these are not traits I  find useful in a public intellectual.

The absence of E.O. Wilson (or Noam Chomsky) from the list was explained by The Guardian as due to his lack of influence in the last twelve months:
To qualify for this year's world thinkers rankings, it was not enough to have written a seminal book, inspired an intellectual movement or won a Nobel prize several years ago (hence the absence from the 65-strong long list of ageing titans such as Noam Chomsky or Edward O Wilson); the selectors' remit ruthlessly insisted on "influence over the past 12 months" and "significance to the year's biggest questions".
It's also a little disappointing to see Steven Pinker at #3 and Slavoj Žižek at #6. However, it is heartening to see Daniel Kahneman at #10. I would have expected to see Thomas Nagel (Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature Is Almost Certainly False) on this list somewhere - his latest book created a lot of serious discussion about the ability of science to provide answers in every realm of our lives.

World Thinkers 2013

by Prospect / APRIL 24, 2013

The results of Prospect’s world thinkers poll

Left to right: Ashraf Ghani, Richard Dawkins, Steven Pinker 
After more than 10,000 votes from over 100 countries, the results of Prospect’s world thinkers 2013 poll are in. Online polls often throw up curious results, but this top 10 offers a snapshot of the intellectual trends that dominate our age.


1. Richard Dawkins
When Richard Dawkins, the Oxford evolutionary biologist, coined the term “meme” in The Selfish Gene 37 years ago, he can’t have anticipated its current popularity as a word to describe internet fads. But this is only one of the ways in which he thrives as an intellectual in the internet age. He is also prolific on Twitter, with more than half a million followers—and his success in this poll attests to his popularity online. He uses this platform to attack his old foe, religion, and to promote science and rationalism. Uncompromising as his message may be, he’s not averse to poking fun at himself: in March he made a guest appearance on The Simpsons, lending his voice to a demon version of himself.

2. Ashraf Ghani
Few academics get the chance to put their ideas into practice. But after decades of research into building states at Columbia, Berkeley and Johns Hopkins, followed by a stint at the World Bank, Ashraf Ghani returned to his native Afghanistan to do just that. He served as the country’s finance minister and advised the UN on the transfer of power to the Afghans. He is now in charge of the Afghan Transition Coordination Commission and the Institute for State Effectiveness, applying his experience in Afghanistan elsewhere. He is already looking beyond the current crisis in Syria, raising important questions about what kind of state it will eventually become.

3. Steven Pinker
Long admired for his work on language and cognition, the latest book by the Harvard professor Steven Pinker, The Better Angels of Our Nature, was a panoramic sweep through history. Marshalling a huge range of evidence, Pinker argued that humanity has become less violent over time. As with Pinker’s previous books, it sparked fierce debate. Whether writing about evolutionary psychology, linguistics or history, what unites Pinker’s work is a fascination with human nature and an enthusiasm for sharing new discoveries in accessible, elegant prose.

4. Ali Allawi
Ali Allawi began his career in 1971 at the World Bank before moving into academia and finally politics, as Iraq’s minister of trade, finance and defence after the fall of Saddam Hussein. Since then he has written a pair of acclaimed books, most recently The Crisis of Islamic Civilisation, and he is currently a senior visiting fellow at Princeton. “His scholarly work on post-Saddam Iraq went further than anyone else has yet done in helping us understand the complex reality of that country,” says Clare Lockhart, co-author (with Ashraf Ghani) of Fixing Failed States. “His continuing work on the Iraqi economy—and that of the broader region—is meanwhile helping to illuminate its potential, as well as pathways to a more stable and productive future.”

5. Paul Krugman
As a fierce critic of the economic policies of the right, Paul Krugman has become something like the global opposition to fiscal austerity. A tireless advocate of Keynesian economics, he has been repeatedly attacked for his insistence that government spending is critical to ending the recession. But as he told Prospect last year, “we’ve just conducted what amounts to a massive experiment on pretty much the entire OECD [the industrialised world]. It’s been as slam-dunk a victory for a more or less Keynesian view as one can possibly imagine.” His New York Times columns are so widely discussed that it is easy to overlook his academic work, which has won him a Nobel prize and made him one of the world’s most cited economists.

6. Slavoj Žižek
Slavoj Žižek’s critics seem unsure whether to dismiss him as a buffoon or a villain. The New Republic has called him “the most despicable philosopher in the west,” but the Slovenian’s legion of fans continues to grow. He has been giving them plenty to chew on—in the past year alone he has produced a 1,200-page study of Hegel, a book, The Year of Dreaming Dangerously, analysing the Arab Spring and other recent events, and a documentary called The Pervert’s Guide to Ideology. And he has done all this while occupying academic posts at universities in Slovenia, Switzerland and London. His trademark pop culture references (“If you ask me for really dangerous ideological films, I’d say Kung Fu Panda,” he told one interviewer in 2008) may have lost their novelty, but they remain a gentle entry point to his studies of Lacanian psychoanalysis and left-wing ideology.

7. Amartya Sen
Amartya Sen will turn 80 in November—making him the fourth oldest thinker on our list—but he remains one of the world’s most active public intellectuals. He rose to prominence in the early 1980s with his studies of famine. Since then he has gone on to make major contributions to developmental economics, social choice theory and political philosophy. Receiving the Nobel prize for economics in 1998, he was praised for having “restored an ethical dimension to the discussion of vital economic problems.” The author of Prospect’s first cover story in 1995, Sen continues to write influential essays and columns, in the past year arguing against European austerity. And he shows no sign of slowing down or narrowing his focus—his latest book (with Jean Drèze), An Uncertain Glory: India and its Contradictions, will be published in July.

8. Peter Higgs
The English physicist Peter Higgs lent his name to the Higgs boson, the subatomic particle discovered last year at Cern that gives mass to other elementary particles. Although Higgs is always quick to point out that others were involved in early work on the existence of the particle, he was central to the first descriptions of the boson in 1964. “Of the various people who contributed to that piece of theory,” Higgs told Prospect in 2011, “I was the only one who pointed to this particle as something that would be… of interest for experimentalists.” Higgs is expected to receive a Nobel prize this year for his achievements.

9. Mohamed ElBaradei
The former director general of the UN’s international atomic energy agency and winner of the 2005 Nobel peace prize, Mohamed ElBaradei has become one of the most prominent advocates of democracy in Egyptian politics over the past two years. Since December, ElBaradei has been the coordinator of the National Salvation Front, a coalition of political parties dedicated to opposing what they see as President Mohamed Morsi’s attempts to secure power for himself and impose a new constitution favouring Islamist parties. Reflecting widespread concern about Morsi’s actions, ElBaradei has accused the president of appointing himself “Egypt’s new pharaoh.”

10. Daniel Kahneman
Since the publication of Thinking, Fast and Slow in 2011, Daniel Kahneman has become an unlikely resident at the top of the bestseller lists. His face has even appeared on posters on the London Underground, with only two words of explanation: “Thinking Kahneman.” Although he is a psychologist by training, his work on our capacity for making irrational decisions helped create the field of behavioural economics, and he was awarded the Nobel prize for economics in 2002. His book has now brought these insights to a wider audience, making them more influential than ever.

Biographies by Daniel Cohen, Jay Elwes and David Wolf. Additional research by Luke Neima and Lucy Webster


11. Steven Weinberg, physicist
12. Jared Diamond, anthropolgist
13. Oliver Sacks, psychologist
14. Ai Weiwei, artist
15. Arundhati Roy, writer
16. Nate Silver, statistician
17. Asgar Farhadi, filmmaker
18. Ha-Joon Chang, economist
19. Martha Nussbaum, philosopher
20. Elon Musk, businessman
21. Michael Sandel, philosopher (see below)
22. Niall Ferguson, historian
23. Hans Rosling, statistician
24 = Anne Applebaum, journalist
24 = Craig Venter, biologist
26. Shinya Yamanaka, biologist
27. Jonathan Haidt, psychologist
28. George Soros, philanthropist
29. Francis Fukuyama, political scientist
30. James Robinson and Daron Acemoglu, political scientist and economist
31. Mario Draghi, economist
32. Ramachandra Guha, historian
33. Hilary Mantel, novelist
34. Sebastian Thrun, computer scientist
35. Zadie Smith, novelist
36 = Hernando de Soto, economist
36 = Raghuram Rajan, economist
38. James Hansen, climate scientist
39. Christine Lagarde, economist
40. Roberto Unger, philosopher
41. Moisés Naím, political scientist
42. David Grossman, novelist
43. Andrew Solomon, writer
44. Esther Duflo, economist
45. Eric Schmidt, businessman
46. Wang Hui, political scientist
47. Fernando Savater, philosopher
48. Alexei Navalny, activist
49. Katherine Boo, journalist
50. Anne-Marie Slaughter, political scientist
51. Paul Collier, development economist
52. Margaret Chan, health policy expert
53. Sheryl Sandberg, businesswoman
54. Chen Guangcheng, activist
55. Robert Shiller, economist
56 = Ivan Krastev, political scientist
56 = Nicholas Stern, economist
58. Theda Skocpol, sociologist
59 = Carmen Reinhart, economist
59 = Ngozi Okonjo-Iweala, economist
61. Jeremy Grantham, investment strategist
62. Thomas Piketty and Emmanuel Saez, economists
63. Jessica Tuchman Mathews, political scientist
64. Robert Silvers, editor
65. Jean Pisani-Ferry, economist


Only three thinkers from our 2005 top 10, Richard Dawkins, Paul Krugman and Amartya Sen, appear in this year’s top spots. The panelists who drew up the longlist of 65 gave credit for the currency of candidates’ work—their influence over the past 12 months and their continuing significance for this year’s biggest questions.

Among the new entries at the top are Peter Higgs—whose inclusion is a sign of public excitement about the discoveries emerging from the world’s largest particle physics laboratory, Cern—and Slavoj Žižek, whose critique of global capitalism has gained more urgency in the wake of the financial crisis. The appearance of Steven Pinker and Daniel Kahneman, authors of two of the most successful recent “ideas books,” further demonstrates the public appetite for serious, in-depth thinking in the age of the TED talk. The inclusion of Ashraf Ghani, Ali Allawi and Mohamed ElBaradei—from Afghanistan, Iraq and Egypt, respectively—reflects the importance of their work on fostering democracies across the Muslim world in the wake of foreign interventions and the Arab Spring.

One new development was the influence of social media, with just over half of voters coming to the world thinkers homepage via Twitter or Facebook. Twitter also gave readers a chance to respond to the list and highlight notable omissions—Stephen Hawking and Noam Chomsky were popular choices.

As always, the absences are as revealing as the familiar names at the top. The failure of environmental thinkers to win many votes may be a sign of the faltering energy of the green movement. Despite the presence of climate scientists lower down the list, the movement seems to lack successors to influential public intellectuals such as Rachel Carson and James Lovelock. Serious thinkers about the internet and technology are also conspicuous by their absence. The highest-placed representative of Silicon Valley is the entrepreneur Elon Musk, but beyond journalist-critics such as Evgeny Morozov and Nicholas Carr, technology still awaits its heavyweight public intellectuals (see Thomas Meaney, £).

Most striking of all is the lack of women at the top of this year’s list. The highest-placed woman in this year’s poll, at number 15, is Arundhati Roy, who has become a prominent left-wing critic of inequalities and injustice in modern India since the publication of her novel The God of Small Things over a decade ago.

Many thanks to all those who voted. Do let us know what you make of the results.

David Wolf


Thursday, April 25, 2013

Steve Silberman - Neurodiversity Rewires Conventional Thinking About Brains

Not all brains are created equal, which is a good thing. But based on the pharmaceutical industry's desire to have us all taking pills that homogenize us, you would never be able to tell that neurodiversity is an evolutionary advantage.

This article from Wired Magazine looks at the origins and popularization of neurodiversity.

Neurodiversity Rewires Conventional Thinking About Brains

By Steve Silberman | April 16, 2013


In the late 1990s, a sociologist named Judy Singer—who is on the autism spectrum herself—invented a new word to describe conditions like autism, dyslexia, and ADHD: neurodiversity. In a radical stroke, she hoped to shift the focus of discourse about atypical ways of thinking and learning away from the usual litany of deficits, disorders, and impairments. Echoing positive terms like biodiversity and cultural diversity, her neologism called attention to the fact that many atypical forms of brain wiring also convey unusual skills and aptitudes.

Autistic people, for instance, have prodigious memories for facts, are often highly intelligent in ways that don’t register on verbal IQ tests, and are capable of focusing for long periods on tasks that take advantage of their natural gift for detecting flaws in visual patterns. By autistic standards, the “normal” human brain is easily distractible, is obsessively social, and suffers from a deficit of attention to detail. “I was interested in the liberatory, activist aspects of it,” Singer explained to journalist Andrew Solomon in 2008, “to do for neurologically different people what feminism and gay rights had done for their constituencies.”

The new word first appeared in print in a 1998 Atlantic article about Wired magazine’s website, HotWired, by journalist Harvey Blume. “Neurodiversity may be every bit as crucial for the human race as biodiversity is for life in general,” he declared. “Who can say what form of wiring will prove best at any given moment? Cybernetics and computer culture, for example, may favor a somewhat autistic cast of mind.

Thinking this way is no mere exercise in postmodern relativism. One reason that the vast majority of autistic adults are chronically unemployed or underemployed, consigned to make-work jobs like assembling keychains in sheltered workshops, is because HR departments are hesitant to hire workers who look, act, or communicate in non-neurotypical ways—say, by using a keyboard and text-to-speech software to express themselves, rather than by chattering around the water cooler.

One way to understand neurodiversity is to remember that just because a PC is not running Windows doesn’t mean that it’s broken. Not all the features of atypical human operating systems are bugs. We owe many of the wonders of modern life to innovators who were brilliant in non-neurotypical ways. Herman Hollerith, who helped launch the age of computing by inventing a machine to tabulate and sort punch cards, once leaped out of a school window to escape his spelling lessons because he was dyslexic. So were Carver Mead, the father of very large scale integrated circuits, and William Dreyer, who designed one of the first protein sequencers.

Singer’s subversive meme has also become the rallying cry of the first new civil rights movement to take off in the 21st century. Empowered by the Internet, autistic self-advocates, proud dyslexics, unapologetic Touretters, and others who think differently are raising the rainbow banner of neurodiversity to encourage society to appreciate and celebrate cognitive differences, while demanding reasonable accommodations in schools, housing, and the workplace.

A nonprofit group called the Autistic Self Advocacy Network is working with the US Department of Labor to develop better employment opportunities for all people on the spectrum, including those who rely on screen-based devices to communicate (and who doesn’t these days?). “Trying to make someone ‘normal’ isn’t always the best way to improve their life,” says ASAN cofounder Ari Ne’eman, the first openly autistic White House appointee.

Neurodiversity is also gaining traction in special education, where experts are learning that helping students make the most of their native strengths and special interests, rather than focusing on trying to correct their deficits or normalize their behavior, is a more effective method of educating young people with atypical minds so they can make meaningful contributions to society. “We don’t pathologize a calla lily by saying it has a ‘petal deficit disorder,’” writes Thomas Armstrong, author of a new book called Neurodiversity in the Classroom. “Similarly, we ought not to pathologize children who have different kinds of brains and different ways of thinking and learning.”

In forests and tide pools, the value of biological diversity is resilience: the ability to withstand shifting conditions and resist attacks from predators. In a world changing faster than ever, honoring and nurturing neurodiversity is civilization’s best chance to thrive in an uncertain future.

Zen Brain - Greed and Generosity: The Neuroscience and Path of Transforming Addiction

From Upaya Zen Center, here is another great series of Zen Brain lectures, featuring many of the usual participants, including Joan Halifax Roshi, Al Kaszniak, Lawrence Barsalou, David Loy, and Do-On Robert Thomas.

This series is focused on Greed and Generosity: The Neuroscience and Path of Transforming Addiction.

Zen Brain - Greed and Generosity: The Neuroscience and Path of Transforming Addiction

Series Description: Buddhism recognizes attachment/desire as one of the three “poisons” or afflictions at the root of suffering. In modern Western culture, a consumer economy and the lure of constant, technology-mediated connection fuel our sense of lack and addictions to such things as shopping and the internet. Zen provides a path of liberation from attachment, aversion, and delusion through practice realization of the interdependent, impermanent nature of life, with no fixed, unchanging self at its core.

Recently, neuroscience has provided insights into the plasticity of reward circuitry and chemistry in the brain, as related to attraction and addiction. In this retreat, a philosopher, a neuroscientist, and a Roshi, all of whom are Zen teachers, will explore the relationship of these new scientific discoveries to Buddhist psychology, Zen practice and the challenges of living in a consumerist and technology-driven culture.

Joan Halifax & Al Kaszniak: 04-12-2013: ZEN BRAIN: Greed and Generosity – The Neuroscience and Path of Transforming Addiction (Part 1)

Episode Description: In this, the opening session of Zen Brain on Greed and Generosity, Roshi Joan starts by offering an overview of the retreat and introduces the members of the panel. Dr. Kaszniak then offers his presentation titled “Addiction and craving: Neuroscientific and Contemplative Clinical Science Perspectives.”

BIO: Joan Halifax Roshi is a Buddhist teacher, Zen priest, anthropologist, and author. She is Founder, Abbot, and Head Teacher of Upaya Zen Center, a Buddhist monastery in Santa Fe, New Mexico. She received her Ph.D in medical anthropology in 1973. She has lectured on the subject of death and dying at many academic institutions, including Harvard Divinity School and Harvard Medical School, Georgetown Medical School, University of Virginia Medical School, Duke University Medical School, University of Connecticut Medical School, among many others. She received a National Science Foundation Fellowship in Visual Anthropology, and was an Honorary Research Fellow in Medical Ethnobotany at Harvard University. From 1972-1975, she worked with psychiatrist Stanislav Grof at the Maryland Psychiatric Research Center on pioneering work with dying cancer patients, using LSD as an adjunct to psychotherapy. After the LSD project, she has continued to work with dying people and their families and to teach health care professionals as well as lay individuals on compassionate care of the dying. She is Director of the Project on Being with Dying and Founder and Director of the Upaya Prison Project that develops programs on meditation for prisoners. For the past twenty-five years, she has been active in environmental work. She studied for a decade with Zen Teacher Seung Sahn and was a teacher in the Kwan Um Zen School. She received the Lamp Transmission from Thich Nhat Hanh, and was given Inka by Roshi Bernie Glassman. A Founding Teacher of the Zen Peacemaker Order, her work and practice for more than three decades has focused on applied Buddhism. Her books include: The Human Encounter with Death (with Stanislav Grof); Shamanic Voices; Shaman: The Wounded Healer; The Fruitful Darkness; Simplicity in the Complex: A Buddhist Life in America; Being with Dying; and Wisdom Beyond Wisdom (with Kazuaki Tanashashi).

Al Kaszniak received his Ph.D. in clinical and developmental psychology from the University of Illinois in 1976, and completed an internship in clinical neuropsychology at Rush Medical Center in Chicago. He is currently Director of the Arizona Alzheimer’s Consortium Education Core, and a professor in the departments of psychology, neurology, and psychiatry at The University of Arizona (UA. He formerly served as Head of the Psychology Department, and as Director of the UA Center for Consciousness Studies. Al also presently serves as Chief Academic Officer for the Mind and Life Institute, an organization that facilitates collaborative scientific research on contemplative practices and traditions. He is the co-author or editor of seven books, including the three-volume Toward a Science of Consciousness (MIT Press), and Emotions, Qualia, and Consciousness (World Scientific). His research, published in over 150 journal articles and scholarly book chapters, has been supported by grants from the U.S. National Institute on Aging, National Institute of Mental Health, and National Science Foundation, as well as several private foundations. His work has focused on the neuropsychology of Alzheimer’s disease and other age-related neurological disorders, consciousness, memory self-monitoring, emotion, and the psychophysiology of long-term and short-term meditation. Al has served on the editorial boards of several scientific journals, and has been an advisor to the National Institutes of Health and other governmental agencies. He is a Past-President of the Section on Clinical Geropsychology and fellow of the American Psychological Association and a fellow of the Association for Psychological Science. In addition to his academic and administrative roles, he is a lineage holder and teacher (Sensei) in the Soto tradition of Zen Buddhism.


The Compassionate Brain - The Power of Self-Compassion w/ Kristin Neff

Kristin Neff, PhD, is an associate professor at the University of Texas, Austin, and is the author of Self-Compassion: Stop Beating Yourself Up and Leave Insecurity Behind (Morrow, 2011). She has been practicing Buddhist meditation since 1997, and has co-created a program on Mindful Self-Compassion with her associate Chris Germer at Harvard University.
In addition to her book, she has also created an audio program with Sounds True, Self-Compassion, Step by Step (A Six-Session Training Course for Transforming Your Relationship with Yourself).

The audio (and video) below is from a Sounds True series by Rick Hanson on The Compassionate Brain.

The Compassionate Brain, Session 6: The Power of Self-Compassion

A FREE eight-part video series, hosted by Dr. Rick Hanson, that explores effective ways to change your brain and heart and life.

(Watch or listen to the entire series by registering at

Session Highlights:

 The Power of Self-Compassion [ 1:04:02 ] Hide Player | Play in Popup | Download
Recorded session with Dr. Rick Hanson and Dr. Kristin Neff
Play the live session from Monday, November 12, 2012 

Rick Hanson, Ph.D., is a neuropsychologist and author of Buddha’s Brain: The Practical Neuroscience of Happiness, Love, and Wisdom (in 23 languages) and Just One Thing: Developing a Buddha Brain One Simple Practice at a Time (in 12 languages). Founder of the Wellspring Institute for Neuroscience and Contemplative Wisdom and Affiliate of the Greater Good Science Center at UC Berkeley, he’s been an invited speaker at Oxford, Stanford, and Harvard, and taught in meditation centers worldwide. His work has been featured on the BBC, NPR, Fox Business, Consumer Reports Health, U.S. News and World Report, and O Magazine and he has several audio programs with Sounds True. His weekly e-newsletter - Just One Thing – has over 72,000 subscribers, and suggests a simple practice each week that will bring you more joy, more fulfilling relationships, and more peace of mind and heart. If you wish, you can subscribe to Just One Thing here.

Wednesday, April 24, 2013

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome

Not everyone who uses SSRI antidepressants goes through painful, debilitating withdrawals upon ceasing their use. But for those who, the "Discontinuation Syndrome" can be disabling and crazy-making.

This article from Frontiers in Neuropharmacology looks at the evidence and details which drugs are more likely to cause symptoms - the shorter the half-life (the time it takes for the drug to reach half its original potency), the worse the withdrawal symptoms.

It's open access, so I am posting the entire article - please share with those who might need the information.

Full Citation: 
Renoir T. (2013). Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved. Frontiers in Neuropharmacology. 4:45. doi: 10.3389/fphar.2013.00045

Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved

Thibault Renoir
  • Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC, Australia

Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition.


Selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of depressive disorders (Petersen et al., 2002; Chaudhry et al., 2011) and anxiety disorders (van der Linden et al., 2000; Hedges et al., 2007). Total SSRI prescription volume increased threefold between 1995/1996 and 2006/2007 (Lockhart and Guthrie, 2011). Despite this, the use of SSRIs is not without flaws. Apart from potential adverse side effects arising from long-term antidepressant treatment, as well as issues of relapse, and recurrence following remission of a depressive episode (Rucci et al., 2011; Rush et al., 2012), the existence of a SSRI discontinuation syndrome (also known as SSRI withdrawal syndrome) has been suggested in some cases. A decade ago, Harvey et al. (2003) highlighted that although significant progress had been made to uncover the pathophysiology of depression and the mechanisms of actions of SSRIs, the neurobiology of SSRI discontinuation syndrome had not been comprehensively addressed. Following an overview of the clinical evidence, we will discuss the possible molecular mechanisms implicated in the pathology of SSRI discontinuation syndrome, and comment on the use of animal models to better understand this condition.
Clinical Evidence of SSRI Discontinuation Syndrome

About 15 years ago, Zajecka et al. (1997) proposed a definition of the SSRI discontinuation syndrome as the onset of a cluster of symptoms following the discontinuation of a SSRI, not attributable to other causes (i.e., concomitant medication, illness). Along with sensory and gastrointestinal symptoms, the SSRI discontinuation syndrome includes somatic symptoms such as dizziness, lethargy, and sleep disturbances, as well as psychological symptoms such as anxiety/agitation, irritability, and poor concentration (Warner et al., 2006; Haddad and Anderson, 2007). The literature on these symptoms initially consisted mainly of case reports (Coupland et al., 1996;Price et al., 1996; Schatzberg et al., 1997; Bryois et al., 1998; Goldstein et al., 1999). Haddad (1997) reviewed 47 separate reports of SSRI discontinuation syndrome, 30 of which involved paroxetine compared to only seven involving fluoxetine, despite the latter being prescribed more frequently. Black et al. (2000) identified 53 different symptoms within the condition (with dizziness being the most common) and proposed a diagnostic criteria for SSRI discontinuation syndrome that requires two or more of the described symptoms developing within 1–7 days of discontinuation (or reduction in dosage) of an SSRI after at least 1 month of treatment.

These case reports have since been followed up by a number of controlled studies (i.e., prospective studies, with a randomized, double-blind interruption period, which included a systematic method for discontinuation symptoms data collection). For example, using the Discontinuation Emergent Signs and Symptoms (DESS) checklist, Rosenbaum et al. (1998)assessed the effects of a 1-week placebo substitution period in patients diagnosed with unipolar depressive disorder who had been maintained on fluoxetine, sertraline, or paroxetine for similar periods of time (∼11 months). Following treatment interruption, there was a significant increase in the number of DESS items observed in the sertraline- and paroxetine-treated patients. In contrast, this was not detected in fluoxetine-treated patients. Another double-blind trial found that placebo substitution for paroxetine was associated with increased frequency and severity of specific physical and psychological symptoms, which arose as early as after the second missed dose (Michelson et al., 2000). In that trial, patients with a history of depression had been undergoing SSRI treatment for similar periods of time (∼12–15 months) and were equivalent on several parameters (e.g., similar baseline symptom severity). The discontinuation symptoms seemed to be specific to paroxetine in this study, since patients treated with sertraline or fluoxetine did not exhibit discontinuation syndrome within the 5-day placebo substitution period. However, since sertraline and fluoxetine (but not paroxetine) have active metabolites with half-lives around 2–3 and 7–15 days respectively (Table 1), the effects of longer withdrawal periods are worth assessing in future studies. In the case of fluoxetine, it is possible that discontinuation symptoms may emerge when the levels of the active metabolite decrease after 15 days and beyond. Consistent with that possibility, Zajecka et al. (1998) found a small increase in reports of dizziness among patients who discontinued fluoxetine 4 and 6 weeks after placebo substitution. Bogetto et al. (2002) investigated 97 outpatients diagnosed with dysthymic disorder who were instructed to stop their medication (paroxetine or fluoxetine) after a successful treatment period of at least 8 weeks. With a mean time of onset of symptoms of 2 days after drug discontinuation, discontinuation syndrome was reported by 27% of patients (of which 85% had been treated with paroxetine compared to only 15% treated with fluoxetine). Analyzing randomized controlled studies of escitalopram and paroxetine for the treatment of anxiety disorders (in which treatments were followed by a prospectively defined discontinuation period), Baldwin et al. (2007) reported that individuals taking either SSRI showed more discontinuation symptoms compared to placebo. Following a 12–24 week treatment period, patients were abruptly switched to placebo and were assessed using the DESS checklist 1 and 2 weeks after drug cessation. Overall, paroxetine withdrawal induced significantly more discontinuation symptoms than escitalopram.
Table 1. Pharmacokinetic and pharmacological parameters of SSRIs (adapted from Hiemke and Hartter, 2000; Owens et al., 1997, 2001; Tatsumi et al., 1997).
There are a variety of symptoms associated with paroxetine withdrawal asMurata et al. (2010) recently provided based on observations of a group of Japanese outpatients (n = 56). These symptoms included dizziness (50% of patients), increased dreaming/vivid dreams (35%), fatigue (30%), nausea/vomiting (30%), headache (25%), anxiety/agitation (25%), paresthesia (15%), insomnia (10%), diarrhea (10%), visual disturbances (10%), fever (10%), tremor (5%), irritability (5%), and chills (5%). In addition to these symptoms, in an assessment of 87 patients who had their treatment interrupted for 4–7 days in a double-blind placebo study,Hindmarch et al. (2000) also reported greater cognitive deficits, poorer quality of sleep and increased depressive symptoms associated with paroxetine discontinuation, symptoms which were not evident in patients ceasing fluoxetine, sertraline, or citalopram treatment.

To date, there is no evidence to suggest that the length of SSRI treatment is associated with the development of more symptoms or with the severity of those symptoms (Rosenbaum et al., 1998; Michelson et al., 2000;Baldwin et al., 2007). However, several studies suggest that an abrupt interruption of treatment results in more symptoms of the discontinuation syndrome compared to a gradual tapering of the drug (van Geffen et al., 2005; Himei and Okamura, 2006; Murata et al., 2010). This suggests that the incidence, timing, and severity of SSRI discontinuation symptoms may be related to plasma elimination characteristics of each drug. In view of this, Michelson et al. (2000) found a statistically significant relationship between the percentage reduction in plasma concentration of the drug and the appearance of discontinuation symptoms resulting from placebo substitution across all drug groups (fluoxetine, sertraline, and paroxetine). Comparing drug concentrations before and after placebo substitution,Henry et al. (2000) found that lower steady-state brain levels of paroxetine (but not fluoxetine) after placebo substitution were associated with greater risk for discontinuation-related adverse events. Overall, discontinuation symptoms are more frequent after the abrupt cessation of drugs with shorter half-lives (Rosenbaum et al., 1998; Bogetto et al., 2002;Judge et al., 2002; Baldwin et al., 2007). However, that relationship may not be an absolute predictor. Indeed, despite paroxetine having a similar half-life to that of fluvoxamine, the rate of withdrawal reactions for the latter drug is 10 times lower (Price et al., 1996). For example, in the 46 patients with discontinuation symptoms reviewed by Black et al. (2000), paroxetine was stopped in 65% of these cases compared to only 7% of cases with fluvoxamine. To date, there are no double-blind trials with placebo substitution comparing the effects of discontinuation from paroxetine and fluvoxamine, and the higher number of reports of withdrawal reactions with paroxetine is likely to reflect the greater prescription rate of paroxetine over fluvoxamine (Lockhart and Guthrie, 2011). Other factors (i.e., pharmacological) could also contribute to the high frequency of discontinuation syndrome with paroxetine.

Notably, paroxetine has significant off-target effects, including an affinity for cholinergic receptors similar to the tricyclic antidepressants (Owens et al., 1997, 2001), raising the possibility for a cholinergic rebound during discontinuation. Fujishiro et al. (2002) further demonstrated that the ability of paroxetine to induce an anticholinergic effect in mice was similar to that of tricyclic antidepressants, whereas fluvoxamine was much less potent in that regard. Paroxetine also exhibits moderately high affinity for the norepinephrine transporter, unlike other SSRIs (Tatsumi et al., 1997). In comparison, the longer half-lives of the active compounds of fluoxetine and sertraline may be the reason underlying fewer symptoms of the discontinuation syndrome. However, as raised previously, the major limitation of most of the clinical studies examining the discontinuation syndrome is the restriction of treatment interruption to only few days, when longer periods (i.e., weeks) might be more suitable for the study of fluoxetine withdrawal. Finally, whether or not the pharmacodynamic characteristics of a drug could also help to explain the clinical observations remains to be addressed. For instance, fluoxetine is also a 5-HT2C receptor antagonist (Sanchez and Hyttel, 1999) with affinity for 5-HT2A/2Creceptors (see Table 1), whereas sertraline is the sole SSRI which also inhibits the dopamine transporter (Tatsumi et al., 1997).

The discontinuation syndrome has been reported in relation to nearly every SSRI, although there are increased reports of occurrence in patients ceasing treatment of paroxetine. However, the full extent of discontinuation syndrome might only emerge if future studies are designed to take into account the pharmacokinetics of the drug and availability of its active metabolite. Double-blind trials with placebo substitution have yet to be undertaken to directly compare the effects of discontinuation from SSRIs with shorter half-lives (i.e., paroxetine and fluvoxamine). Overall, the crucial question of whether the discontinuation syndrome is equally related to the lack of specificity and/or the neurobiology related to the half-life of the SSRI remains unclear. Potential genetic-drug interactions should also be systematically assessed in future studies. Indeed, a recent clinical study suggested a possible involvement of the C(-1019)G polymorphism of the serotonin 5-HT1A receptor gene in the occurrence of paroxetine discontinuation syndrome, as patients with the −1019C allele experienced paroxetine discontinuation syndrome more frequently than patients who were −1019G homozygous (Murata et al., 2010).

Animal Studies

Mechanisms of Action of SSRIs

Numerous laboratories have studied the effects of SSRIs on the serotonergic system, mainly investigating on the pharmacological characteristics of these drugs (Table 1). For example, using intracerabral microdialysis in conscious rodents, extracellular concentrations of serotonin have been reported to be increased following acute administration of fluoxetine (Hervas and Artigas, 1998), citalopram (Rea et al., 2010), or sertraline (Kitaichi et al., 2010). Further, Sharp et al. (1997) showed that paroxetine induced a larger increase in extracellular serotonin in the frontal cortex when serotonin autoreceptors on both the somatodendrites (5-HT1A) and nerve terminals (5-HT1B) were blocked. Incidentally, the acute effects of SSRIs on serotonin neurotransmission are controlled by several feedback mechanisms, which include 5-HT1A and 5-HT1B/1D autoreceptors (Malagie et al., 2001; Pullar et al., 2004) as well as postsynaptic 5-HT2receptors (Boothman et al., 2003; Cremers et al., 2004; Calcagno et al., 2009). Recent discoveries suggest an unexpected complexity in the mechanisms controlling the activity of serotonin neurons (Sharp et al., 2007).

Notably, and particularly relevant to this review, antidepressant drugs typically require chronic administration (i.e., several weeks) to achieve therapeutic efficacy. This delay is thought to partly reflect the time required for autoreceptors to desensitize so as to facilitate serotonin neurotransmission (Kreiss and Lucki, 1995). Rather than the desensitization per se, Le Poul et al. (1995) suggested that the progressive increase in the number of serotonergic neurons with desensitized 5-HT1Aautoreceptors may play a critical role in the slow development of the antidepressant actions of SSRIs. Extensive research has been done to study the changes to serotonergic signaling induced by chronic SSRI administration (summarized in Table 2).
Table 2. Summary of the main serotonergic adaptive changes during chronic administration versus discontinuation from SSRIs (in animal models).
Although it was initially thought that the antidepressant effects of SSRIs were solely attributable to an increase in brain serotonin, more recent evidence suggests that a sustained increase in serotonin levels (at least within the hippocampus) does not appear to be required for the beneficial anxiolytic/antidepressant-like effects of chronic fluoxetine (Popa et al., 2010). Studies have now shown that SSRIs modulate other neurochemical signaling systems in the brain such as noradrenaline and dopamine. For instance, paroxetine was reported to increase extracellular levels of noradrenaline in the hippocampus of rats that had received repeated administration of the drug (Hajos-Korcsok et al., 2000). Similarly, chronic (but not acute) treatment with fluoxetine potentiates dopamine D2/D3 receptor function (Collu et al., 1997; Dziedzicka-Wasylewska et al., 2002). Therefore, it has now become evident that in addition to effects at receptors regulating monoamine release (e.g., 5-HT1, 5-HT2, and α-2 adrenergic receptors), multiple targets (e.g., glutamate/GABA, peptidergic systems, neurotrophic factors, hypothalamic-pituitary-adrenal axis, etc.) are likely to be involved in the mechanism of action of SSRIs (Schechter et al., 2005; Renoir et al., 2012). With that in mind, we next review the effects of SSRI treatment discontinuation in animal models. Most of these reports have focused on the serotonergic system. However, as mentioned, there is scope for future studies to assess non-serotonin signaling pathways in relation to the SSRI discontinuation syndrome.

Effects of SSRI Treatment Discontinuation in Animal Models

In this section we first focus on the few animal studies which report behavioral changes after cessation of SSRI treatment (versus behavioral changes found during treatment), followed by a discussion of the potential molecular mechanisms involved. Despite the relatively consistent cluster of clinical symptoms observed in the SSRI discontinuation syndrome, few animal studies have been conducted to explicitly examine the effects of withdrawal from chronic SSRI treatment. Moreover, most of those studies have used fluoxetine, despite a low incidence of discontinuation syndrome associated with this specific SSRI in the clinic.

In one animal study, contrasting with the reduction of locomotor activity observed during chronic administration of fluoxetine (30 mg/kg/day for 5 days), fluoxetine-treated rats showed a significant increase in locomotor activity upon discontinuation (Bjork et al., 1998). Notably, this “rebound effect” was only observed during the first 4 h following the first “missed” dose, and not during the subsequent washout period. These findings suggest that upon cessation of chronic fluoxetine, rats showed an increase in activity resembling withdrawal behavior, in line with the symptoms of anxiety/agitation reported by some patients who develop the discontinuation syndrome. Hyperactivity in response to abrupt fluoxetine discontinuation may result from fluoxetine’s effects on the dopaminergic system, specifically in the ventral tegmental area and in the nucleus accumbens. In that regard, Gardier et al. (1994) found that chronic fluoxetine treatment caused a persistent decrease in striatal dopamine levels lasting up to 14 days after treatment discontinuation. Other reports have provided further evidence of changes in dopaminergic signaling during SSRI discontinuation. By measuring the spontaneous firing rate of hippocampal CA1 neurons, Bijak and Smialowski (1988) found that the excitatory reaction evoked by the selective D1 receptor agonist SKF-38393 was potentiated following repeated citalopram administration, and was further increased after drug withdrawal. Similarly, the enhancement of dopaminergic synaptic modulation (through hippocampal D1 receptor upregulation) induced by chronic fluoxetine was maintained for 1 month after drug withdrawal (Kobayashi et al., 2012). The mesolimbic dopamine system is thought to be involved in the behavioral effects of antidepressants (Collu et al., 1997), as well as in the withdrawal syndrome following cessation of drugs of abuse (Hu, 2007; D’Souza and Markou, 2010; Radke et al., 2011). However, another animal study found no change in intracranial self-stimulation threshold during withdrawal from chronic fluoxetine treatment (Lin et al., 1999). This finding suggests that there is no change in central reward function after cessation of fluoxetine treatment, and therefore that SSRI discontinuation syndrome and withdrawal symptoms in drug addiction may involve distinct pathways. However, since several clinical observations point to the existence of tolerance phenomena during antidepressant treatment in some cases (Fava and Offidani, 2011), further animal research is required to determine the dependence potential of the various types of antidepressant drugs.

In an attempt to compare and contrast the mechanisms underlying the effects of continuous SSRI administration against abrupt SSRI discontinuation, Bosker and colleagues measured the acoustic startle response of rats that had either been receiving 2 weeks of citalopram or had undergone 48 h of discontinuation from citalopram treatment (Bosker et al., 2010). Behavioral assessments started 2 days after the removal of osmotic mini pumps filled with either saline or 50 mg/ml citalopram. Habituation was significantly diminished in the 48-h discontinuation group, as their acoustic startle response (a transient motor response to an unexpected, intensive stimulus) was significantly greater compared to the rats receiving ongoing 2 week citalopram treatment. Exaggerated acoustic startle response has been previously linked to anxiety-like behaviors in rodents (Plappert and Pilz, 2002). Therefore, the findings of Bosker et al. (2010) suggest a higher level of anxiety in the citalopram discontinuation group, which is similar to the increased incidence of anxiety in patients with the SSRI discontinuation syndrome. An increased reactivity to acoustic stimuli in rats has been linked to long-term depletion of serotonin in the brain (Tanke et al., 2008). Consistent with that notion, Bosker et al. (2010)found that an index of serotonin turnover [the ratio of 5-hydroxyindoleacetic acid to serotonin (5-HIAA/5-HT)] was increased after the 48-h washout period following chronic citalopram treatment, while chronic treatment exerted no significant effect on serotonin turnover. This finding is in agreement with an earlier study reporting that levels of the serotonin metabolite 5-HIAA are increased during withdrawal from chronic fluoxetine (30 mg/kg/days for 21 days), and are sustained at levels exceeding control levels (by 30–50%) for at least 14 days after cessation of chronic fluoxetine treatment (Trouvin et al., 1993). Similarly, while serotonin turnover rates were significantly decreased during the first 24 h after the last injection of a 3-week treatment with fluoxetine (6.9 mg/kg/day), turnover rates increased significantly after an 8-day washout period (Stenfors and Ross, 2002). Behavioral changes in relation to increased serotonin turnover rates during drug washout were not examined. Similarly, as Bosker et al. (2010) assessed the biochemical consequences and behavioral effects of citalopram discontinuation in separate cohorts of animals, no direct comparisons between increased serotonin turnover and increased acoustic startle response could be made. Further behavioral testing is required to validate the finding of a greater acoustic startle response, using additional tests such as the elevated-plus maze, the light-dark box, etc. Finally, based on the low incidence of the discontinuation syndrome reported in patients treated with citalopram or fluoxetine, it is likely that studying the role of serotonin turnover in the behavioral effects of long-term paroxetine administration versus discontinuation might give different results. Indeed, likely resulting from the accumulation of its main active metabolite norfluoxetine after 14 days of chronic administration, only fluoxetine (but not paroxetine)-treated animals exhibited reduced brain serotonin levels after a 1-week washout period (Caccia et al., 1993).

Despite the fact that adaptive changes in 5-HT1A/1B autoreceptors are critically involved in the mechanistic actions of SSRIs (as discussed in See Mechanisms of Action of SSRIs), many preclinical studies of SSRI withdrawal have focused on serotonin levels. As such, a lack of understanding of any possible adaptive functional changes to serotonin receptors remains. Raap et al. (1999) reported that 5-HT1A receptors located in the hypothalamus of rats are desensitized following a 2-week treatment with fluoxetine, an effect which lasted for at least 60 days. Given the implications of the fronto-cortical regions and the hippocampus in the withdrawal symptoms, and based on altered serotonin metabolism mentioned in the previous section, further work is required to improve our understanding of the extent of 5-HT1A receptor adaptation in the brain following SSRI withdrawal. One study suggested that molecular changes follow a rapid time course, requiring 3–14 days of washout to reverse the reductive effects of chronic fluoxetine and paroxetine treatment on pre-synaptic 5-HT1B receptor mRNA levels in rat dorsal raphe nucleus (Anthony et al., 2000).

Although not the main focus of the studies, two separate groups reported the behavioral effects of long-term administration of paroxetine compared to the behavioral effects of discontinuation of paroxetine treatment (Gervasoni et al., 2002; Elizalde et al., 2008). It was found that the anxiolytic-like effects of chronic paroxetine (10 mg/kg/day for 3 weeks) were no longer observed after a 2-week washout period (Elizalde et al., 2008). The loss of this drug effect is interesting considering the development of symptoms of anxiety in patients with the discontinuation syndrome. On the other hand, the antidepressant effect of paroxetine and the amelioration of cognitive deficits were maintained even after a 2-week washout period, which does not correspond with increased incidence of depressive symptoms in individuals experiencing the discontinuation syndrome. While this study was not designed to explicitly examine the discontinuation syndrome, to our knowledge this is the sole preclinical study assessing the longer term behavioral effects of halting chronic SSRI treatment in an animal model of depression (i.e., chronic mild stress paradigm). As the eventual development of the discontinuation syndrome was not the focus of the study, other behavioral parameters relevant to the clinical symptoms of the syndrome, such as changes in sleep patterns/architecture, were not examined. Gervasoni et al. (2002)reported that in rats, a reduction in the amount of REM sleep, as well as an increase in the duration of REM sleep episodes, was associated with chronic treatment with paroxetine (5 mg/kg/day for 21 days), rather than to discontinuation of treatment, as these sleep changes were not observed after a 24-h washout period. Since sleep disturbances are often reported in patients with discontinuation symptoms, it is of importance for future animal studies examining the discontinuation syndrome to assess sleep patterns/architecture as relevant outcomes.

Overall, the number of preclinical studies looking at the effects of SSRI after a washout period remains very limited. Many such reports were published prior to the recognition of SSRI discontinuation syndrome as a clinical condition, and were mainly intended to study the mechanism of action of the SSRI while having the drug on board. To date, clear discontinuation-like behaviors in animal models have not yet been reported. However, it should be noted that we suggest that a flaw of these previous studies did not use animal models of depression. In addition, it is of importance that future studies consider an appropriate time point for assessment based on the half-life of the drug of interest. It is also of importance for future studies to examine the effects of paroxetine, as this SSRI has been implicated in numerous clinical cases of the discontinuation syndrome (Bogetto et al., 2002; Judge et al., 2002; Baldwin et al., 2007). The animal studies performed to date have focused on measures of tissue serotonin levels; as it is now clear that other pathways are involved in the mechanistic actions of SSRIs, future investigations should be broadened to include an examination of these additional actions. The complex nature of SSRI discontinuation syndrome, in terms of the variety of subtle symptoms that may present at the clinic, poses a challenge for preclinical studies, and there is a need for appropriate animal models to be developed in order to facilitate further study of the behavioral aspects of this condition. As mentioned, the majority of studies to date have been based on “normal” animals, whereas the clinical population who develop the discontinuation syndrome are typically taking SSRIs for treatment of depression, anxiety, etc. As such, future studies of the SSRI discontinuation syndrome in rodents should encompass well-established animal models of depression, chronic SSRI treatment, followed by an appropriate period of drug withdrawal.

Discussion and Conclusion

Although initial observations relied only on case reports, there is now a substantial body of clinical evidence suggesting that, in some cases, SSRIs may be associated with a withdrawal response when halted after a period of regular use. The existence of these symptoms, known as the SSRI discontinuation syndrome, has now been confirmed by a number of well-controlled studies (i.e., double-blind randomized placebo-controlled design, in which treatment is followed by a prospectively defined discontinuation period). These studies suggest that the best route of action for cessation of SSRI treatment is to taper down the dose of the medication rather than abrupt termination, as tapering is likely to decrease the possibility of the occurrence of discontinuation symptoms. Due to the broad range of symptoms which can develop as part of the discontinuation syndrome, prior to drug initiation, patients and caregivers need to be provided with adequate education and realistic, objective appraisals of possible outcomes which can develop during and following antidepressant treatment.

The current evidence suggests that the discontinuation syndrome is dependent on the SSRI half-life, with more reports of symptoms occurring in patients treated with paroxetine compared to other SSRIs. However, studies designed to assess the onset of discontinuation syndrome, and how the syndrome coincides temporally with pharmacokinetic withdrawal, are still lacking. Such studies are critical in order to draw conclusions when comparing SSRIs with short versus long half-lives. It is currently unclear as to whether the discontinuation syndrome is equally related to the pharmacological properties of a given SSRI, and/or its half-life. Future studies could also examine possible associations of the syndrome with clinical characteristics, as one study reported that the discontinuation syndrome was more common in patients with earlier onset of dysthymic disorder, and was also more common in females (Bogetto et al., 2002). On the other hand, Baldwin et al. (2007) reported no difference in discontinuation symptoms in patients with depression compared to patients with anxiety disorders. Future clinical investigations need to have enough statistical power to enable examination of within-group comparisons. Current understanding of the pathophysiology associated with the SSRI discontinuation syndrome remains largely speculative (Blier and Tremblay, 2006; Delgado, 2006). In fact, the sole clinical investigation looking at the possible chemical and molecular mechanisms underlying the SSRI discontinuation syndrome was based on a single subject (Kaufman et al., 2003).

Notably, not all patients treated with SSRIs (which represents a very heterogeneous population) experience discontinuation symptoms. In that regard, a recent clinical study indicated a possible involvement of the C(-1019)G polymorphism of the serotonin 5-HT1A receptor gene in the occurrence of paroxetine discontinuation syndrome (Murata et al., 2010). Whether the development of discontinuation symptoms has a genetic component requires additional studies to provide more conclusive results. The use of genetic animal models might be able to shed light in that regard. Interestingly, using mice with higher (1A-High) or lower (1A-Low) autoreceptor levels, Richardson-Jones et al. (2010) found a negative relationship between 5-HT1A autoreceptor level and response to antidepressants. Further studies looking at the effects of 5-HT1A receptor function on vulnerability to the discontinuation syndrome are of interest. Most of the animal studies performed thus far have naturally focused on the serotonergic system, and have mainly used fluoxetine, despite the fact that this specific SSRI has been associated with a lower incidence of discontinuation syndrome in the clinic. However, based on the numerous targets known to be changed adaptively during chronic treatment with SSRIs in animal models, further studies assessing non-serotonergic pathways would be worthwhile. Finally, preclinical studies using appropriate animal models of anxiety/depression are still lacking when it comes to the study of SSRI discontinuation.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The author would like to thank Drs. Terence Pang and Xin Du for their assistance in improving manuscript editing, as well as the reviewers for their valuable comments and suggestions.

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