Ursolic Acid for Cancer Prevention and Treatment

There is a new natural substance (well, not really new) that has been getting serious attention from the cancer research world. Ursolic Acid has been around for more than a decade, but it the last few years its prominence as a chemopreventive agent has increased considerably.

Via Wikipedia (follow the links for citation information):

Ursolic acid (sometimes referred to as 3-beta-3-hydroxy-urs-12-ene-28-oic-acid or 3-β-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpene acid capable of inhibiting various cancer cell types by inhibiting the STAT3 activation pathway,[2][3] one of which includes human fibrosarcoma by reducing expression of matrix metalloproteinase-9 via glucocorticoid receptors. It may also decrease proliferation of cancer cells and induce apoptosis.[4] Ursolic acid has also been shown to inhibit JNK expression and IL-2 activation of JURKAT leukemic T Cells leading to the reduction in proliferation and T cell activation.[5] Ursolic acid is present in many plants, including apples, basil, bilberry, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, and prunes. Apple peels contain large quantities of ursolic acid and related compounds.[6]

Ursolic acid can serve as a starting material for synthesis of more potent bioactive derivatives, such as antitumor agents.[7] It has been found to reduce muscle atrophy and to stimulate muscle growth in mice.[8][9] Ursolic acid has potential use as a cardioprotective compound.[10]

Ursolic acid was found to be a weak aromatase inhibitor (IC50 = 32 μM).[11]

Ursolic acid has been shown to increase the amount of muscle and brown fat and decrease white fat obesity and associated conditions when added to diets fed to mice.[12]

If you look for this in health food stores, most of the supplements you'll find are from apple skins or from basil and rosemary. The problem with these supplements is that ursolic acid content is relatively low. For example, NOW Foods Holy Basil Extract (2% standardized) only offers 10 mg per 500 mg capsule; Nature's Way Holy Basil Extract (2.5% standardized) only offers 11.25 mg per 450 mg capsule.

However, in the sports supplement world, this substance has been known for a while as a potential aromatase inhibitor (aromatase converts testosterone to estrogen, especially when T levels are too high) and as a possible "nutrient partitioning" agent (switches metabolism from fat storage to muscle building in the presence of weight training and excess calories). Supplements in this area are dosed much higher: Urso-X contains 600 mg of rosemary leaf per two-capsule dose, being 25% ursolic acid, or 150 mg of ursolic acid per two-capsules; Ursolix is dosed at 225 mg of ursolic acid per 3 capsules (Holy Basil extract, 25% standardized).

Cancer Research

Over the last ten or so years, there has been an increasing amount of research into the use of ursolic acid (or modified pharmaceutical versions of the molecule) in treating and preventing cancer. It turns out that ursoic acid has potent chemopreventive properties.

A study last year (March, 2012) showed that ursolic acid inhibits the initiation and progression of Prostate Cancer by modulating pro-Inflammatory pathways. This puts ursolic acid in the same top tier category as curcumin and resveratrol (the two best researched and validated natural chemopreventive supplements for prostate cancer.

A more recent article (May, 2013) showed that ursolic acid simultaneously targets multiple signaling pathways to suppress proliferation and induce apoptosis (programmed cell death) in colon cancer cells.

Finally, a study from June, 2012, looked at how ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance, and fatty liver disease in mice fed a high-fat diet with ursolic acid. The results were striking:

[U]rsolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis.

First up, the two cancer articles, then last the article the ergogenic and metabolic effects of ursolic acid. All of these articles are Open Access via PLoS ONE.

Ursolic Acid Inhibits the Initiation, Progression of Prostate Cancer and Prolongs the Survival of TRAMP Mice by Modulating Pro-Inflammatory Pathways

Muthu K. Shanmugam, Tina H. Ong, Alan Prem Kumar, Chang K. Lun, Paul C. Ho, Peter T. H. Wong, Kam M. Hui, Gautam Sethi

Abstract

Prostate cancer is one of the leading causes of cancer death among men worldwide. In this study, using transgenic adenocarcinoma of mouse prostate (TRAMP) mice, the effect of diet enriched with 1% w/w ursolic acid (UA) was investigated to evaluate the stage specific chemopreventive activity against prostate cancer. We found that TRAMP mice fed with UA diet for 8 weeks (weeks 4 to 12) delayed formation of prostate intraepithelial neoplasia (PIN). Similarly, mice fed with UA diet for 6 weeks (weeks 12 to 18) inhibited progression of PIN to adenocarcinoma as determined by hematoxylin and eosin staining. Finally, TRAMP mice fed with UA diet for 12 weeks (weeks 24 to 36) demonstrated markedly reduced tumor growth without any significant effects on total body weight and prolonged overall survival. With respect to the molecular mechanism, we found that UA down-regulated activation of various pro-inflammatory mediators including, NF-κB, STAT3, AKT and IKKα/β phosphorylation in the dorsolateral prostate (DLP) tissues that correlated with the reduction in serum levels of TNF-α and IL-6. In addition, UA significantly down-regulated the expression levels of cyclin D1 and COX-2 but up-regulated the levels of caspase-3 as revealed by immunohistochemical analysis of tumor tissue sections. Finally, UA was detected in serum samples obtained from various mice groups fed with enriched diet in nanogram quantity indicating that it is well absorbed in the GI tract. Overall, our findings provide strong evidence that UA can be an excellent agent for both the prevention and treatment of prostate cancer.

Full Citation: 

Shanmugam MK, Ong TH, Kumar AP, Lun CK, Ho PC, et al. (2012). Ursolic Acid Inhibits the Initiation, Progression of Prostate Cancer and Prolongs the Survival of TRAMP Mice by Modulating Pro-Inflammatory Pathways. PLoS ONE 7(3): e32476. doi:10.1371/journal.pone.0032476

* * * * * * *

Ursolic Acid Simultaneously Targets Multiple Signaling Pathways to Suppress Proliferation and Induce Apoptosis in Colon Cancer Cells

Jingshu Wang, Liqun Liu, Huijuan Qiu, Xiaohong Zhang, Wei Guo, Wangbing Chen, Yun Tian, Lingyi Fu, Dingbo Shi, Jianding Chengl, Wenlin Huang, Wuguo Deng

Abstract

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid distributed in medical herbs, exerts antitumor effects and is emerging as a promising compound for cancer prevention and therapy, but its excise mechanisms of action in colon cancer cells remains largely unknown. Here, we identified the molecular mechanisms by which UA inhibited cell proliferation and induced apoptosis in human colon cancer SW480 and LoVo cells. Treatment with UA led to significant inhibitions in cell viability and clone formation and changes in cell morphology and spreading. UA also suppressed colon cancer cell migration by inhibiting MMP9 and upregulating CDH1 expression. Further studies showed that UA inhibited the phosphorylation of Akt and ERK proteins. Pretreatment with an Akt or ERK-specific inhibitor considerably abrogated the proliferation inhibition by UA. UA also significantly inhibited colon cancer cell COX-2 expression and PGE2 production. Pretreatment with a COX-2 inhibitor (celecoxib) abrogated the UA-induced cell proliferation. Moreover, we found that UA effectively promoted NF-κB and p300 translocation from cell nuclei to cytoplasm, and attenuated the p300-mediated acetylation of NF-κB and CREB2. Pretreatment with a p300 inhibitor (roscovitine) abrogated the UA-induced cell proliferation, which is reversed by p300 overexpression. Furthermore, UA treatment induced colon cancer cell apoptosis, increased the cleavage of PARP, caspase-3 and 9, and trigged the release of cytochrome c from mitochondrial inter-membrane space into cytosol. These results indicate that UA inhibits cell proliferation and induces apoptosis in colon cancer cells through simultaneous modulation of the multiple signaling pathways such as MMP9/CDH1, Akt/ERK, COX-2/PGE2, p300/NF-κB/CREB2, and cytochrome c/caspase pathways.

Full Citation: 

Wang J, Liu L, Qiu H, Zhang X, Guo W, et al. (2013) Ursolic Acid Simultaneously Targets Multiple Signaling Pathways to Suppress Proliferation and Induce Apoptosis in Colon Cancer Cells. PLoS ONE 8(5): e63872. doi:10.1371/journal.pone.0063872

* * * * * * *

Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease 

Steven D. Kunkel, Christopher J. Elmore, Kale S. Bongers, Scott M. Ebert, Daniel K. Fox, Michael C. Dyle, Steven A. Bullard, Christopher M. Adams

Abstract

Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

Full Citation: 

Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, et al. (2012) Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease. PLoS ONE 7(6): e39332. doi:10.1371/journal.pone.0039332

From NPR's On Being with Krista Tippett, this is a nice interview with Sounds True founder and CEO, Tami Simon. Sounds True is the single best resource we have for audio teachings (as well as books and some video sessions) by the world's leading spiritual teachers from a variety of backgrounds and disciplines.

Tami Simon produced the Kosmic Consciousness course with Ken Wilber many years ago, which was my introduction to her as an interviewer and Sounds True as a company. More recent offerings include Robert Augustus Masters's Knowing Your Shadow and Pema Chodron's How to Meditate, among many other excellent offerings.

Not only do I love Sounds True and what it offers, but having Spoken to Tami a couple of times, she is someone whose vision and integrity I respect enormously.

INNER LIFE AT WORK: TAMI SIMON ON BUSINESS, MEDITATION, AND TECHNOLOGY

This Week's Conversation with Krista Tippett

May 30, 2013

You might call Tami Simon a spiritual entrepreneur. She's built a successful multimedia publishing company with a mission to disseminate "spiritual wisdom" by diverse teachers and thinkers like Pema Chödrön and Eckhart Tolle, Daniel Goleman and Brené Brown. She offers compelling lessons on joining inner life with life in the workplace — and advice on spiritual practice with a mobile device.

Listen

• Radio Show/Podcast - (mp3, 51:00)
• Unedited Interview, Tami Simon (mp3, 87:25)

Learn

• Books + Music
• Transcript

Voices on the Radio

Tami Simon is the publisher and CEO of the multimedia publishing company Sounds True and hosts a weekly podcast series called Insights at the Edge.

Pertinent Posts from the On Being Blog

The Work We Value, The Intelligence We Ignore: Is the Work that Made America Great Valued Any Longer?  "The skills gap is a reflection of what we value. To close the gap, we need to change the way the country feels about work." ~Mike Rowe

What Would You Be Willing to Sacrifice?  A video that's so heartbreakingly gorgeous and unswerving in its emotional sway, it'll have you pondering your own station in life.

A Little Bit of Mindfulness Meditation Can Reduce a Lot of Pain  Even novice meditators are able to curb their pain after a few training sessions in mindfulness meditation.

From Bookfourm's Omnivore blog, a collection of links on physics, cosmology, and the metaphysics of the universe.

Fundamental physics is in a metaphysical mess

MAY 30 2013

1:00PM

• From Edge, Lee Smolin on thinking about nature and how to make a theory of the universe as a whole system. 
• James Gleick reviews Time Reborn: From the Crisis in Physics to the Future of the Universe by Lee Smolin. 
• Lisa Randall’s Guide to the Galaxy: The famed cosmologist unveils her latest theories on the invisible universe, extra dimensions and human consciousness. 
• Dark matter is the commonest, most elusive stuff there is — can we grasp this great unsolved problem in physics? 
• Big news from the annals of science last week: A British newspaper reports that the mysteries of the universe may have been solved by a hedge-fund economist who left academia 20 years ago. 
• Jon F. Wilkins on Eric Weinstein and an outsider’s Theory of Everything. 
• Philosophy isn't dead yet: Far from having replaced metaphysics, fundamental physics is in a metaphysical mess and needs help — Einstein saw it coming.

Most studies one reads on depression are examining the benefits or effects of antidepressant medications on depression, and sometimes they even analyze the added benefits of medication with psychotherapy (usually CBT).

In this new study from PLos MED, researchers looked at how seven different types of "talk therapy" (interpersonal psychotherapy, behavioural activation, cognitive behavioural therapy, problem solving therapy, psychodynamic therapy, social skills training and supportive counselling) and how they impact subjective experience of depression. According to the study, they all performed equally well:  "Overall, we found that different psychotherapeutic interventions for depression have comparable, moderate-to-large effects."

That's good news for those who would rather not deal with the troubling and sometimes disabling side effects of antidepressant medications.

On a related side note there are several studies suggesting that psychodynamic/psychoanalytic therapy continues to decrease symptoms and increase well-being even after leaving therapy (Jonathan Shedler, [2009], The Efficacy of Psychodynamic Psychotherapy). This would seem to give an advantage to that form of therapy over the other six used in the study.

Full Citation:
Barth J, Munder T, Gerger H, Nüesch E, Trelle S, et al. (2013). Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis. PLoS Med 10(5): e1001454. doi:10.1371/journal.pmed.1001454

Different Types of Psychotherapy Have Similar Benefits for Depression

May 28, 2013 — Treatments for depression that don't involve antidepressant drugs but rather focus on different forms of talking therapy (referred to as psychotherapeutic interventions) are all beneficial, with no one form of therapy being better than the others, according to a study by international researchers published in this week's PLOS Medicine.

These findings are important as they suggest that patients with depression should discuss different forms of non-drug therapy with their doctors and explore which type of psychotherapy best suits them.

The researchers, led by Jürgen Barth from the University of Bern in Switzerland, reached these conclusions by reviewing 198 published studies involving over 15,000 patients receiving one of seven types of psychotherapeutic intervention: Interpersonal psychotherapy, behavioural activation, cognitive behavioural therapy, problem solving therapy, psychodynamic therapy, social skills training and supportive counselling (definitions of each type of therapy are below). The authors compared each of the therapies with each other and with a control -- patients on a waiting list or continuing usual case -- and combined the results.

The authors found that all seven therapies were better at reducing symptoms of depression than waiting list and usual care and that there were no significant differences between the different types of therapy. They also found that the therapies worked equally well for different patient groups with depression, such as for younger and older patients and for mothers who had depression after having given birth. Furthermore, the authors found no substantial differences when comparing individual with group therapy or with face-to-face therapy compared with internet-based interactions between therapist and patient.

The authors say: "We found evidence that most of the seven psychotherapeutic interventions under investigation have comparable effects on depressive symptoms and achieve moderate to large effects vis-à-vis waitlist."

They continue: "All seven psychotherapeutic interventions achieved a small to moderate effect compared to usual care."

The authors add: "Overall, we found that different psychotherapeutic interventions for depression have comparable, moderate-to-large effects."

Notes:

"Interpersonal psychotherapy" is short and highly structured, using a manual to focus on interpersonal issues in depression.

"Behavioral activation" raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment.

"Cognitive behavioural therapy" focuses on a patient's current negative beliefs, evaluates how they affect current and future behaviour, and attempts to restructure the beliefs and change the outlook. "Problem solving therapy" aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution.

"Psychodynamic therapy" focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation.

In "social skills therapy," patients are taught skills that help to build and maintain healthy relationships based on honesty and respect.

"Supportive counselling" is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.

Funding: This research was supported by a Swiss National Science Foundation Grant (no. 105314-118312/1) awarded to JB, HJZ, and PJ.

Here is the beginning of the source research article:

Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis

Jürgen Barth, Thomas Munder, Heike Gerger, Eveline Nüesch, Sven Trelle, Hansjörg Znoj, Peter Jüni, Pim Cuijpers

Abstract

Background

Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.

Methods and Findings

We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = −0.62 to d= −0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = −0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = −0.30, 95% credibility interval [CrI] [−0.54 to −0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [−0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [−0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions. 

Conclusions

Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.

Editors' Summary

Background

Depression is a very common condition. One in six people will experience depression at some time during their life. People who are depressed have recurrent feelings of sadness and hopelessness and might feel that life is no longer worth living. The condition can last for months and often includes physical symptoms such as headaches, sleeping problems, and weight gain or loss. Treatment of depression can include non-drug treatments (psychotherapy), antidepressant drugs, or a combination of the two. Especially for people with mild or intermediate depression, psychotherapy is often considered the preferred first option. Psychotherapy describes a range of different psychotherapies, and a number of established types of psychotherapies have all shown to work for at least some patients.

Why Was This Study Done?

While it is broadly accepted that psychotherapy can help people with depression, the question of which type of psychotherapy works best for most patients remains controversial. While many scientific studies have compared one psychotherapy with control conditions, there have been few studies that directly compared multiple treatments. Without such direct comparisons, it has been difficult to establish the respective merits of the different types of psychotherapy. Taking advantage of a recently developed method called “network meta-analysis,” the authors re-examine the evidence on seven different types of psychotherapy to see how well they have been shown to work and whether some work better than others.

What Did the Researchers Do and Find?

The researchers looked at seven different types of psychotherapy, which they defined as follows. “Interpersonal psychotherapy” is short and highly structured, using a manual to focus on interpersonal issues in depression. “Behavioral activation” raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment. “Cognitive behavioral therapy” focuses on a patient's current negative beliefs, evaluates how they affect current and future behavior, and attempts to restructure the beliefs and change the outlook. “Problem solving therapy” aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution. “Psychodynamic therapy” focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation. In “social skills therapy,” patients are taught skills that help to build and maintain healthy relationships based on honesty and respect. “Supportive counseling” is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.

The researchers started with a systematic search of the medical literature for relevant studies. The search identified 198 articles that reported on such clinical trials. The trials included a total of 15,118 patients and compared one of the seven psychotherapies either with another one or with a common “control intervention”. In most cases, the control (no psychotherapy) was deferral of treatment by “wait-listing” patients or continuing “usual care.” With network meta-analysis they were able to summarize the results of all these trials in a meaningful way. They did this by integrating direct comparisons of several psychotherapies within the same trial (where those were available) with indirect comparisons across all trials (using no psychotherapy as a control intervention).

Based on the combined trial results, all seven psychotherapies tested were better than wait-listing or usual care, and the differences were moderate to large, meaning that the average person in the group that received therapy was better off than about half of the patients in the control group. When comparing the therapies with each other, the researchers saw small or no differences, meaning that none of them really stood out as much better or much worse than the others. They also found that the treatments worked equally well for different patient groups with depression (younger or older patients, or mothers who had depression after having given birth). Similarly, they saw no big differences when comparing individual with group therapy, or person-to-person with internet-based interactions between therapist and patient.

However, they did find that smaller and less rigorous studies generally found larger benefits of psychotherapies, and most of the studies included in the analysis were small. Only 36 of the studies had at least 50 patients who received the same treatment. When they restricted their analysis to those studies, the researchers still saw clear benefits of cognitive-behavioral therapy, interpersonal therapy, and problem-solving therapy, but not for the other four therapies.

What Do these Findings Mean?

Similar to earlier attempts to summarize and make sense of the many study results, this one finds benefits for all of the seven psychotherapies examined, and none of them stood as being much better than some or all others. The scientific support for being beneficial was stronger for some therapies, mostly because they had been tested more often and in larger studies.

Treatments with proven benefits still do not necessarily work for all patients, and which type of psychotherapy might work best for a particular patient likely depends on that individual. So overall this analysis suggests that patients with depression and their doctors should consider psychotherapies and explore which of the different types might be best suited for a particular patient.

The study also points to the need for further research. Whereas depression affects large numbers of people around the world, all of the trials identified were conducted in rich countries and Western societies. Trials in different settings are essential to inform treatment of patients worldwide. In addition, large high-quality studies should further explore the potential benefits of some of therapies for which less support currently exists. Where possible, future studies should compare psychotherapies with one another, because all of them have benefits, and it would not be ethical to withhold such beneficial treatment from patients. 

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1​001454.

• The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish); information on psychotherapy includes information on its most common forms
• The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
• The UK nonprofit Mind provides information on depression, including an explanation of the most common psychotherapies in the UK
• MedlinePlus provides links to other resources about depression (in English and Spanish)
• The UK nonprofit healthtalkonline.org has a unique database of personal and patient experiences on depression

Citation: Barth J, Munder T, Gerger H, Nüesch E, Trelle S, et al. (2013) Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis. PLoS Med 10(5): e1001454. doi:10.1371/journal.pmed.1001454

Competing interests: PJ is an unpaid member of steering group or executive committee of trials funded by Abbott Vascular, Biosensors, Medtronic and St. Jude Medical. CTU Bern, which is part of the University of Bern, has a staff policy of not accepting individual honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by Abbott Vascular, Ablynx, Amgen, AstraZeneca, Biosensors, Biotronic, Boehrhinger Ingelheim, Eisai, Eli Lilly, Exelixis, Geron, Gilead Sciences, Nestlé, Novartis, Novo Nordisc, Padma, Roche, Schering-Plough, St. Jude Medical, and Swiss Cardio Technologies. The other authors declare that no competing interests exist.

Abbreviations: ACT, behavioural activation; CBASP, cognitive behavioural-analysis system of psychotherapy; CBT, cognitive-behavioural therapy; CI, confidence interval; CrI, credibility interval; d, effect size; D, Somer's D; DYN, psychodynamic therapy; ES, d effect size; IPT, interpersonal therapy; k, number of comparisons; M, mean; p, p-value; PLA, placebo; PST, problem solving therapy; SD, standard deviation; SST, social skills training; SUP, supportive counselling; UC, usual care; WL, wait-list; T2, tau square

Daniel Siegel Discusses Mindsight at the Dalai Lama Center

The full title of this conversation is Mindsight: Brain Science and Transformation for You and Your Relationships. The discussion is based on Dr. Siegel's book, Mindsight: The New Science of Personal Transformation (2010).

Mindsight: Brain Science and Transformation for You and Your Relationships

Dalai Lama Center for Peace and Education
Tuesday, May 10, 2011

On May 10, Daniel Siegel visited Vancouver for the closing event to the Dalai Lama Center's spring Speakers Series. The theme to these events has been "Living Compassion Inside and Out" and his discussion on Mindsight was very much on key. For Dr. Siegel, once we see the mind (inside...) we can have more healthy relationships with others (...and out).

Mindsight: Brain Science and Transformation for You and Your Relationships was moderated by Maria LeRose and she begun the evening by asking Dr. Siegel to define the concept of Mindsight.

"The word 'Mindsight' was created inside of me as a life preserver," said Dr. Siegel, who had briefly left Harvard medical school disillusioned and looking for more from his education. "Ultimately, when I went back to school, I said to myself that the only way that I'm going to survive is to realize that some of my teachers are missing some kind of gear in the way their mind works in that they don't see the mind."

Dr. Siegel described this lack as a lack of Mindsight, the ability to see the mind. He would go on to seek out professors who respected the role of the mind, along with the more subjective sides of health care that deal with grief and suffering.

But before we can see the mind, first we should probably ask where the mind resides. That's one of the questions that Dr. Siegel set out to answer.

"The mind is in your body and it's in your relationships. It's not nowhere. It's not a mystery," he said. "The body is the physical mechanism through which energy and information flow. Relationships are the sharing of energy and information."

Once we've located the mind and are aware of its presence, not only in ourselves but in our relationships, Dr. Siegel says we're ready to take the next step in the Mindsight process: "monitoring and modifying".

"You need to monitor energy and information flow in your bodies and in your relationships and then modify it toward integration."

And integration, for Dr. Siegel, occurs when two people can share a connection where each sees the mind of the other. Integration leads to empathic relationships.

Throughout the event, Dr. Siegel touched on a number of topics, ranging from his education as a medical practitioner to his recommendations on how to educate children to have Mindsight. If you missed the discussion, the Dalai Lama Center encourages you to check out either of the video or audio podcasts below.

Here is some more on Mindsight from the book promotion at Amazon:

From a pioneer in the field of mental health comes a groundbreaking book on the healing power of "mindsight," the potent skill that is the basis for both emotional and social intelligence. Mindsight allows you to make positive changes in your brain–and in your life.

• Is there a memory that torments you, or an irrational fear you can' t shake?
• Do you sometimes become unreasonably angry or upset and find it hard to calm down?
• Do you ever wonder why you can't stop behaving the way you do, no matter how hard you try?
• Are you and your child (or parent, partner, or boss) locked in a seemingly inevitable pattern of conflict?

What if you could escape traps like these and live a fuller, richer, happier life? This isn't mere speculation but the result of twenty-five years of careful hands-on clinical work by Daniel J. Siegel, M.D. A Harvard-trained physician, Dr. Siegel is one of the revolutionary global innovators in the integration of brain science into the practice of psychotherapy. Using case histories from his practice, he shows how, by following the proper steps, nearly everyone can learn how to focus their attention on the internal world of the mind in a way that will literally change the wiring and architecture of their brain.

Through his synthesis of a broad range of scientific research with applications to everyday life, Dr. Siegel has developed novel approaches that have helped hundreds of patients heal themselves from painful events in the past and liberate themselves from obstacles blocking their happiness in the present. And now he has written the first book that will help all of us understand the potential we have to create our own lives. Showing us mindsight in action, Dr. Siegel describes

• a sixteen-year-old boy with bipolar disorder who uses meditation and other techniques instead of drugs to calm the emotional storms that made him suicidal
• a woman paralyzed by anxiety, who uses mindsight to discover, in an unconscious memory of a childhood accident, the source of her dread
• a physician–the author himself–who pays attention to his intuition, which he experiences as a "vague, uneasy feeling in my belly, a gnawing restlessness in my heart and my gut," and tracks down a patient who could have gone deaf because of an inaccurately written prescription for an ear infection
• a twelve-year-old girl with OCD who learns a meditation that is "like watching myself from outside myself" and, using a form of internal dialogue, is able to stop the compulsive behaviors that have been tormenting her

These and many other extraordinary stories illustrate how mindsight can help us master our emotions, heal our relationships, and reach our fullest potential.

A book as inspiring as it is informative, as practical as it is profound, Mindsight offers exciting new proof that we aren't hardwired to behave in certain ways, but instead have the ability to harness the power of our minds to resculpt the neural pathways of our brains in ways that will be life-transforming.

Jason Castro - Where Does Identity Come From?

In a rather ingeneous study using mice, researchers looked at 40 genetically identical mice in an enriched environment (an approximately 36 square foot footprint, multi-tiered platforms, nesting boxes, and interconnecting tubes - allowing a more natural set of exploratory behaviors). Since all of the mice are essentially the same mouse, differences in behavioir and character must be contingent on environmental influence and not on their genetics.
Over time, some mice became more adventurous and curious and others less so. When they euthanized the mice, those that were the “wanderers” at the end of the study were also those who experienced the greatest proliferation of adult-born neurons (neurogenesis).

At least some parts of our character (sense of self, or identity) are not accounted for by genetics.

Where Does Identity Come From?

A fascinating new neuroscience experiment probes an ancient philosophical question—and hints that you might want to get out more

May 28, 2013 | By Jason Castro

Imagine we rewound the tape of your life. Your diplomas are pulled off of walls, unframed, and returned. Your children grow smaller, and then vanish. Soon, you too become smaller. Your adult teeth retract, your baby teeth return, and your traits and foibles start to slip away. Once language goes, you are not so much you as potential you. We keep rewinding still, until we’re halving and halving a colony of cells, finally arriving at that amazing singularity: the cell that will become you.

The question, of course, is what happens when we press “play” again. Are your talents, traits, and insecurities so deeply embedded in your genes that they’re basically inevitable? Or could things go rather differently with just a few tiny nudges? In other words, how much of your fate do you allot to your genes, versus your surroundings, versus chance? This is navel gazing that matters.

In the absence of a time rewinder, the next best experiment is to do what Julia Freund and her colleagues did in a simple, yet remarkable recent study. These investigators placed genetically identical individuals (mice in this case) in a common environment, and asked whether systematic behavioral differences could still develop between them. An answer of “Yes” would mean that there are sources of behavioral variability – “individuality,” if you will – that aren’t accounted for by the combination of genes and common environment.

In their experiment, Freund and her colleagues housed 40 genetically identical mice in a so-called “enriched” environment, and monitored their behavior over a period of three months (about 10 to 15 percent of their lifespan) during their early life. The enriched environment was very generous as far as lab-mouse accommodations go, with an approximately 36 square foot footprint, and a multi-tiered arrangement of platforms, nesting boxes, and interconnecting tubes. In these conditions, mice can exhibit a more natural set of exploratory behaviors than in the more typical confining cage.

What made this study different from, say, a study of human twins is that the subjects’ movements could be tracked in extraordinary detail over a significant portion of their lifespan. Each mouse in the study was tagged with a radiofrequency ID (RFID) transponder, whose location was monitored by one of twenty antennas inconspicuously arranged among water bottles, tubes, and nesting boxes. Every movement, chase, and sedentary spell was recorded and logged.

To study potential differences in behavior among the mice, the experimenters used a measure called “roaming entropy.” Basically, this captures how often you get out, and with how much variety. If you’re someone who mostly just darts between work and home, your roaming entropy is low. If you’re the kind of person who could conceivably be just about anywhere at any given time, your roaming entropy is high.

Initially, the mice were fairly uniform in their roaming entropy. As the weeks progressed, however, the population started to diverge, with some mice being markedly more exploratory than others. If we take the tendency to explore as a kind of crude trait, then this is one trait that elaborates over time, in a way that isn’t strictly determined by genes or available resources.

The most interesting part of the study, however, came when the researchers examined the brain changes that paralleled the changes in exploratory behavior. Before ending the experiment, the mice were injected with a compound that’s selectively incorporated into dividing cells, and hence labels adult-born neurons. While most neurons are fashioned during early development, there are a handful of well-studied brain areas in which new neurons are continuously produced even in adulthood.

Strikingly, the mice which were the “wanderers” at the end of the study were also those who experienced the greatest proliferation of adult-born neurons. While the usual caution of correlation not implying causation applies here, the result is still intriguing. Even after the genetic die are cast at conception, and after the bulk of the neural scaffolding is laid down in early life, the brain maintains a trickle of raw potential through its ability to grow a limited number of new neurons. The authors conjecture that these neurons are involved in tailoring and tuning our behaviors, applying context-specific corrections and adjustments to the more hard-coded aspects of our behavior. In their words, the ways in which we live our lives may make us who we are.

How, exactly does this happen? The authors concede that we don’t really know. This is not to discredit them, but simply to acknowledge that any experiment addressing something as profound, contested, and metaphysically tangled as the nature-nurture question is going to generate more questions than answers.

It could be the case, for example, that epigenetic changes, in which experience modifies patterns of gene expression, give rise to different life trajectories. Or perhaps the result is really hard-line determinism in disguise. Though nominally genetically identical, there are still minute genomic differences between inbred mice. Perhaps these are sufficient to give rise to trait differences that elaborate over time. Another question, of course, is how surprised should we be by the differences in roaming entropy that were observed? Are they comparable to what would be seen among less genetically related individuals of the same species? In other words, are we talking about the difference between type A and type B personalities, or just subtle shades of A?

Regardless of these specifics, this experiment is a potent reminder that our lives are a work in progress. If we’re indeed living out a kind of tape, then it seems to be one in which the tracks can be tweaked as they’re read, even if they’re rather deep. As your brain is shaped by the choices you make, there is room for chance and noise – room for you to be unique.

ABOUT THE AUTHOR(S)

Jason Castro is an assistant professor of psychology and neuroscience at Bates College.

Adrian Raine - The Criminal Mind

A month or so ago in the Wall Street Journal, Adrian Raine wrote about the emerging confluence of neuroscience and genetics with the legal system and our ideas of justice. Some forms of violent behavior and criminality have neural correlates in the brain.

I suspect this is not much more than valuable science that is unlikely to change the legal system. Americans are still very embedded in the Old Testament notion of an eye for an eye, and as long as that is true, I would not expect to see any real changes in the legal system.

The Criminal Mind

Advances in genetics and neuroscience are revolutionizing our understanding of violent behavior—as well as ideas about how to prevent and punish crime.

THE SATURDAY ESSAY
April 26, 2013
By ADRIAN RAINE

In studying brain scans of criminals, researchers are discovering tell-tale signs of violent tendencies. WSJ's Jason Bellini speaks with Professor Adrian Raine about his latest discoveries.

The scientific study of crime got its start on a cold, gray November morning in 1871, on the east coast of Italy. Cesare Lombroso, a psychiatrist and prison doctor at an asylum for the criminally insane, was performing a routine autopsy on an infamous Calabrian brigand named Giuseppe Villella. Lombroso found an unusual indentation at the base of Villella's skull. From this singular observation, he would go on to become the founding father of modern criminology.

Lombroso's controversial theory had two key points: that crime originated in large measure from deformities of the brain and that criminals were an evolutionary throwback to more primitive species. Criminals, he believed, could be identified on the basis of physical characteristics, such as a large jaw and a sloping forehead. Based on his measurements of such traits, Lombroso created an evolutionary hierarchy, with Northern Italians and Jews at the top and Southern Italians (like Villella), along with Bolivians and Peruvians, at the bottom.

These beliefs, based partly on pseudoscientific phrenological theories about the shape and size of the human head, flourished throughout Europe in the late 19th and early 20th centuries. Lombroso was Jewish and a celebrated intellectual in his day, but the theory he spawned turned out to be socially and scientifically disastrous, not least by encouraging early-20th-century ideas about which human beings were and were not fit to reproduce—or to live at all.

The racial side of Lombroso's theory fell into justifiable disrepute after the horrors of World War II, but his emphasis on physiology and brain traits has proved to be prescient. Modern-day scientists have now developed a far more compelling argument for the genetic and neurological components of criminal behavior. They have uncovered, quite literally, the anatomy of violence, at a time when many of us are preoccupied by the persistence of violent outrages in our midst.

The field of neurocriminology—using neuroscience to understand and prevent crime—is revolutionizing our understanding of what drives "bad" behavior. More than 100 studies of twins and adopted children have confirmed that about half of the variance in aggressive and antisocial behavior can be attributed to genetics. Other research has begun to pinpoint which specific genes promote such behavior.

Brain-imaging techniques are identifying physical deformations and functional abnormalities that predispose some individuals to violence. In one recent study, brain scans correctly predicted which inmates in a New Mexico prison were most likely to commit another crime after release. Nor is the story exclusively genetic: A poor environment can change the early brain and make for antisocial behavior later in life.

Most people are still deeply uncomfortable with the implications of neurocriminology. Conservatives worry that acknowledging biological risk factors for violence will result in a society that takes a soft approach to crime, holding no one accountable for his or her actions. Liberals abhor the potential use of biology to stigmatize ostensibly innocent individuals. Both sides fear any seeming effort to erode the idea of human agency and free will.

It is growing harder and harder, however, to avoid the mounting evidence. With each passing year, neurocriminology is winning new adherents, researchers and practitioners who understand its potential to transform our approach to both crime prevention and criminal justice.

The genetic basis of criminal behavior is now well established. Numerous studies have found that identical twins, who have all of their genes in common, are much more similar to each other in terms of crime and aggression than are fraternal twins, who share only 50% of their genes.

Donta Page's brain scan, left, shows the reduced functioning of the ventral prefrontal cortex—the area of the brain that helps regulate emotions and control impulses—compared to a normal brain, right.

Donta Page avoided the death penalty based in part on brain pathology. 

In a landmark 1984 study, my colleague Sarnoff Mednick found that children in Denmark who had been adopted from parents with a criminal record were more likely to become criminals in adulthood than were other adopted kids. The more offenses the biological parents had, the more likely it was that their offspring would be convicted of a crime. For biological parents who had no offenses, 13% of their sons had been convicted; for biological parents with three or more offenses, 25% of their sons had been convicted.

As for environmental factors that affect the young brain, lead is neurotoxic and particularly damages the prefrontal region, which regulates behavior. Measured lead levels in our bodies tend to peak at 21 months—an age when toddlers are apt to put their fingers into their mouths. Children generally pick up lead in soil that has been contaminated by air pollution and dumping.

Rising lead levels in the U.S. from 1950 through the 1970s neatly track increases in violence 20 years later, from the '70s through the '90s. (Violence peaks when individuals are in their late teens and early 20s.) As lead in the environment fell in the '70s and '80s—thanks in large part to the regulation of gasoline—violence fell correspondingly. No other single factor can account for both the inexplicable rise in violence in the U.S. until 1993 and the precipitous drop since then.

Lead isn't the only culprit. Other factors linked to higher aggression and violence in adulthood include smoking and drinking by the mother before birth, complications during birth and poor nutrition early in life.

Genetics and environment may work together to encourage violent behavior. One pioneering study in 2002 by Avshalom Caspi and Terrie Moffitt of Duke University genotyped over 1,000 individuals in a community in New Zealand and assessed their levels of antisocial behavior in adulthood. They found that a genotype conferring low levels of the enzyme monoamine oxidase A (MAOA), when combined with early child abuse, predisposed the individual to later antisocial behavior. Low MAOA has been linked to reduced volume in the amygdala—the emotional center of the brain—while physical child abuse can damage the frontal part of the brain, resulting in a double hit.

Brain-imaging studies have also documented impairments in offenders. Murderers, for instance, tend to have poorer functioning in the prefrontal cortex—the "guardian angel" that keeps the brakes on impulsive, disinhibited behavior and volatile emotions.

Of course, not everyone with a particular brain profile is a murderer—and not every offender fits the same mold. Those who plan their homicides, like serial killers, tend to have good prefrontal functioning. That makes sense, since they must be able to regulate their behavior carefully in order to escape detection for a long time.

So what explains coldblooded psychopathic behavior? About 1% of us are psychopaths—fearless antisocials who lack a conscience. In 2009, Yaling Yang, Robert Schug and I conducted structural brain scans on 27 psychopaths whom we had found in temporary-employment agencies in Los Angeles. All got high scores on the Psychopathy Checklist, the "gold standard" in the field, which assesses traits like lack of remorse, callousness and grandiosity. We found that, compared with 32 normal people in a control group, psychopaths had an 18% smaller amygdala, which is critical for emotions like fear and is part of the neural circuitry underlying moral decision-making. In subsequent research, Andrea Glenn and I found this same brain region to be significantly less active in psychopathic individuals when they contemplate moral issues. Psychopaths know at a cognitive level what is right and what is wrong, but they don't feel it.

What are the practical implications of all this evidence for the physical, genetic and environmental roots of violent behavior? What changes should be made in the criminal-justice system?

Let's start with two related questions: If early biological and genetic factors beyond the individual's control make some people more likely to become violent offenders than others, are these individuals fully blameworthy? And if they are not, how should they be punished?

Take the case of Donta Page, who in 1999 robbed a young woman in Denver named Peyton Tuthill, then raped her, slit her throat and killed her by plunging a kitchen knife into her chest. Mr. Page was found guilty of first-degree murder and was a prime candidate for the death penalty.

Working as an expert witness for Mr. Page's defense counsel, I brought him to a lab to assess his brain functioning. Scans revealed a distinct lack of activation in the ventral prefrontal cortex—the brain region that helps to regulate our emotions and control our impulses.

In testifying, I argued for a deep-rooted biosocial explanation for Mr. Page's violence. As his files documented, as a child he suffered from poor nutrition, severe parental neglect, sustained physical and sexual abuse, early head injuries, learning disabilities, poor cognitive functioning and lead exposure. He also had a family history of mental illness. By the age of 18, Mr. Page had been referred for psychological treatment 19 times, but he had never once received treatment. A three-judge panel ultimately decided not to have him executed, accepting our argument that a mix of biological and social factors mitigated Mr. Page's responsibility.

Mr. Page escaped the death penalty partly on the basis of brain pathology—a welcome result for those who believe that risk factors should partially exculpate socially disadvantaged offenders. But the neurocriminologist's sword is double-edged. Neurocriminology also might have told us that Mr. Page should never have been on the street in the first place. At the time he committed the murder, he had been out of prison for only four months. Sentenced to 20 years for robbery, he was released after serving just four years.

What if I had been asked to assess him just before he was released? I would have said exactly what I said in court when defending him. All the biosocial boxes were checked: He was at heightened risk for committing violence for reasons beyond his control. It wasn't exactly destiny, but he was much more likely to be impulsively violent than not.

This brings us to the second major change that may be wrought by neurocriminology: incorporating scientific evidence into decisions about which soon-to-be-released offenders are at the greatest risk for reoffending. Such risk assessment is currently based on factors like age, prior arrests and marital status. If we were to add biological and genetic information to the equation—along with recent statistical advances in forecasting—predictions about reoffending would become significantly more accurate.

In a 2013 study, Kent Kiehl of the University of New Mexico, looking at a population of 96 male offenders in the state's prison system, found that in the four years after their release, those with low activity in the anterior cingulate cortex—a brain area involved in regulating behavior—were twice as likely to commit another offense as those who had high activity in this region. Research soon to be published by Dustin Pardini of the University of Pittsburgh shows that men with a smaller amygdala are three times more likely to commit violence three years later.

Of course, if we can assess criminals for their propensity to reoffend, we can in theory assess any individual in society for his or her criminal propensity—making it possible to get ahead of the problem by stopping crime before it starts. Ultimately, we should try to reach a point where it is possible to deal with repeated acts of violence as a clinical disorder.

Randomized, controlled trials have clearly documented the efficacy of a host of medications—including stimulants, antipsychotics, antidepressants and mood stabilizers—in treating aggression in children and adolescents. Parents are understandably reluctant to have their children medicated for bad behavior, but when all else fails, treating children to stabilize their uncontrollable aggressive acts and to make them more amenable to psychological interventions is an attractive option.

Treatment doesn't have to be invasive. Randomized, controlled trials in England and the Netherlands have shown that a simple fix—omega-3 supplements in the diets of young offenders—reduces serious offending by about 35%. Studies have also found that early environmental enrichment—including better nutrition, physical exercise and cognitive stimulation—enhances later brain functioning in children and reduces adult crime.

Over the course of modern history, increasing scientific knowledge has given us deeper insights into epilepsy, psychosis and substance abuse, and has promoted a more humane perspective. Just as mental disorders were once viewed as a product of evil forces, the "evil" you see in violent offenders today may someday be reformulated as a symptom of a physiological disorder.

There is no question that neurocriminology puts us on difficult terrain, and some wish it didn't exist at all. How do we know that the bad old days of eugenics are truly over? Isn't research on the anatomy of violence a step toward a world where our fundamental human rights are lost?

We can avoid such dire outcomes. A more profound understanding of the early biological causes of violence can help us take a more empathetic, understanding and merciful approach toward both the victims of violence and the prisoners themselves. It would be a step forward in a process that should express the highest values of our civilization.

—Dr. Raine is the Richard Perry University Professor of Criminology, Psychiatry and Psychology at the University of Pennsylvania and author of The Anatomy of Violence: The Biological Roots of Crime, to be published on April 30 by Pantheon, a division of Random House.


A version of this article appeared April 27, 2013, on page C1 in the U.S. edition of The Wall Street Journal, with the headline: The Criminal Mind.

Daniel Siegel - Interpersonal Neurobiology

This is a brief but cool video of Dr. Dan Siegel explaining what interpersonal neurobiology is - courtesy of Portland Professional Counseling Videos.

Interpersonal Neurobiology

Interpersonal Neurobiology, a term coined by Dr. Dan Siegel, studies the way the brain grows and is influenced by personal relationships. Recent studies have confirmed that we are hardwired to connect with one another, and we connect through our emotions. Our brains, bodies, and minds are inseparable from the emotions that animate them. When that connection fails, we experience significant distress.

Normal human development relies on the cultivation of relationships with others to form and nurture the self-regulatory circuits that enable emotion to enrich, rather than enslave, our lives. Emotionally traumatic events can wreak havoc on our family, relationships and psyche, contributing to intense feelings of anxiety, feeling rejected or abandoned, or simply a perpetual dissatisfaction or distrust of close, intimate relationships. However, experiencing truly healthy relationships can become powerful catalysts for the transformations that are at the heart of the healing process.

IPNB explores the potential for healing trauma by using positive and secure influences on the brain. Conditions once thought to be permanent now have the bright potential for healing and growth. If trauma experience can change our neurons and genes, then “positive” experiences can have potential to restore our bodies to emotional and physical health. IPNB explores subtle, non-conscious influences on our experience of others, including implicit memory, mirror neurons, and emotional resonance.

Implicit Memory – Current situations trigger past emotional memories. ” When I sit in this big comfortable chair, it reminds me of when I was a kid and I would sit in my grandfather’s lap and feel safe and warm”. Or ” I get so angry when my wife and I fight it reminds me of when I would go to my room and hear my parents yelling at each other.”

Mirror Neurons – nerve cells activate in sympathy and in the same brain location as nerve cells of the person whose actions we are watching. These neurons help us to sense what others intend and help us connect with what the other feels…We resonate with their state.

Emotional Resonance – when two people experience deep feelings and can sense what the other feels. A mutual caring that is exchanged through words, expressions, or tones. One can feel what another is feeling.

What a IPNB therapist does:

1. Initiates and creates emotional safety along with the client.
2. Demonstrates vulnerability through transparency and self revealing.
3. Assists client in moving from “talking about” situations to being in emotional exchange with therapist in the “hear and now”.

Selected Books by Daniel Siegel MD

• Mindsight: The New Science of Personal Transformation
• The Mindful Therapist: A Clinician's Guide to Mindsight and Neural Integration (Norton Series on Interpersonal Neurobiology)
• The Developing Mind, Second Edition: How Relationships and the Brain Interact to Shape Who We Are
• The Mindful Brain: Reflection and Attunement in the Cultivation of Well-Being
• Pocket Guide to Interpersonal Neurobiology: An Integrative Handbook of the Mind (Norton Series on Interpersonal Neurobiology)


More video talks by Daniel Siegel MD

Robert Kegan - The Further Reaches of Adult Development: Thoughts on the ‘Self-Transforming’ Mind

Professor Robert Kegan (Harvard) stopped The RSA recently to speak about The Further Reaches of Adult Development: Thoughts on the ‘Self-Transforming’ Mind. Kegan is a developmental psychologist and the William and Miriam Meehan Professor in Adult Learning and Professional Development at Harvard Graduate School of Education. He also is the Educational Chair for the Institute for Management and Leadership in Education and the Co-director for the Change Leadership Group. He is a licensed psychologist and practicing therapist, lectures widely to professional and lay audiences, and consults in the area of professional development.

Kegan is the author of several books, including The Evolving Self: Problem and Process in Human Development (1982), In Over Our Heads: The Mental Demands of Modern Life (1994), How the Way We Talk Can Change the Way We Work: Seven Languages for Transformation (2002), and Immunity to Change: How to Overcome It and Unlock the Potential in Yourself and Your Organization (Leadership for the Common Good) (2009).

In the chart below (adapted from In Over Our Heads), the S stands for Subject (the perceiving self) while the O stands for the Object (the self perceived). The object self is always developmentally lower thn the subject self.

Order of consciousness	Cognitive development	Interpersonal development	Intrapersonal development
(1)	S: PERCEPTIONS;fantasy O: movement	S: SOCIAL PERCEPTIONS O: nothing	S: IMPULSES O: sensation
(2)	S: CONCRETE;actuality; data, cause-and-effect O: perceptions	S: POINT OF VIEW; role-concept; simple reciprocity (tit-for-tat) O: social perceptions	S: ENDURING DISPOSITIONS; needs, preferences, self-concept O: impulses
(3) Traditionalism	S: ABSTRACTIONS;ideality; inference, generalization, hypothesis, proposition, ideals, values O: concrete	S: MUTUALITY / INTERPERSONALISM; role consciousness, mutual reciprocity O: point of view	S: INNER STATES; subjectivity, self-consciousness O: enduring dispositions, preferences, needs
(4) Modernism	S: ABSTRACT SYSTEMS; ideology; formulation, authorization, relations between abstractions O: abstractions	S: INSTITUTION; relationship-regulating forms, multiple-role consciousness O: mutuality / interpersonalism	S: SELF-AUTHORSHIP; self-regulation, self-formation, identity, autonomy, individuation O: inner states, subjectivity, self-consciousness
(5) Post-modernism	S: DIALECTICAL; trans-ideological / post-ideological; testing formulation, paradox, contradiction, oppositeness O: abstract system, ideology	S: INTER-INSTITUTIONAL; relationship between forms; interpenetration of self and other O: institution, relationship-regulating forms	S: SELF-TRANSFORMATION; interpenetration of selves, inter-individuation O: self-authorship, self-regulation, self-formation

With that little bit of background, here is the talk from The RSA.

The Further Reaches of Adult Development: Thoughts on the ‘Self-Transforming’ Mind

23rd May 2013 

Listen to the audio 

(full recording including audience Q&A)
Please right-click link and choose "Save Link As..." to download audio file onto your computer.

There will an edited high-res video version of the talk available in a couple of weeks time, and if you subscribe to our channel on YouTube - you'll get automatically notified whenever there's a new video.

RSA Keynote

Robert Kegan has spent a lifetime studying the development of adult meaning-making or consciousness. His theory of an evolving succession of increasingly encompassing “mindsets” has influenced theory and practice in multiple disciplines on every continent. In a special talk at the RSA, he will address what he has learned about the highest stage in his model, the “self-transforming mind.”

Is it really possible to grow beyond the self-possession and psychological independence of the “self-authoring mind,” so often seen as the zenith of adult development? Is this the province only of a select few human exemplars, or might such capacities be more widely present? What difference does such capacity actually make? And how much does the world need it?

Speaker: Robert Kegan, Meehan Professor of Adult Learning and Professional Development at the Harvard University Graduate School of Education

Chair: Jonathan Rowson, director, RSA Social Brain Centre