While I Was Away...

While I was (mostly) away from the internet, I missed over a week of online excitement. These items are old news by now, but in case you've forgotten...

(1) NPR Morning Edition had a piece on acutely administered ketamine for the treatment of depression:

Could A Club Drug Offer 'Almost Immediate' Relief From Depression?

There's no quick fix for severe depression.

Although antidepressants like Prozac have been around since the 1970s, they usually take weeks to make a difference. And for up to 40 percent of patients, they simply don't work.

As a result, there are limited options when patients show up in an emergency room with suicidal depression.

The doctors and nurses at Ben Taub General Hospital in Houston say they see this problem every day.

More from NPR: 'I Wanted To Live': New Depression Drugs Offer Hope For Toughest Cases.

Other media outlets followed suit. ABC: Ketamine: Quick Fix for Severe Depression? CBS: Club drug ketamine cures depression instantly: How? But why the sudden interest in ketamine and its mechanism of action? Here's an NIMH press release from Tuesday, July 24, 2007:

Faster-Acting Antidepressants Closer to Becoming a Reality
Experimental medication ketamine relieves depression in just hours; points to targets for new medications

A visit to clinicaltrials.gov found 38 studies in a search for 'ketamine depression', starting with the NIMH study first posted in 2004. Twenty-two of these are still (or soon-to-be) recruiting patients, including Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder and the study covered by NPR, Optimization of IV Ketamine for Treatment Resistant Depression. Perhaps someone at Ben Taub Hospital knows someone at NPR (or vice versa)?

Not everyone thinks this dissociative anesthetic/club drug/animal tranquilizer is a great antidepressant. The Neurocritic covered both sides of the story in Ketamine for Depression: Yay or Neigh? as well as a questionable treatment regimen in Chronic Ketamine for Depression: An Unethical Case Study? On a mechanistic level, the mTOR (mammalian target of rapamycin) protein kinase pathway, which is rapidly activated by ketamine, may have its ups and downs. Although activation of mTOR leads to the beneficial effect of increased synaptogenesis in the medial prefrontal cortex (Li et al., 2010), it can also cause accelerated tumor growth, as recently noted by Yang et al., 2011 ("Be prudent of ketamine in treating resistant depression in patients with cancer").

What if you were depressed 10 yrs ago, tried ketamine but didn't know it was supposed to instantly "cure" your depression, and then ended up merely frightened by the K-hole and not better at all? Has that happened to anyone? The anti-ketamine bandwagon is being led by Gawker and its stable of experienced ketamine users:

Super Powerful Club Drug Cures Depression Instantly

Neuropsychiatric researchers say that although traditional antidepressants can take weeks to work, depressed patients who are given BANANAS 'PAUSE BUTTON ON YOUR BRAIN' K-HOLE-INDUCING CLUB DRUG KETAMINE A.K.A. SPECIAL K feel relief from their depression "almost instantly." But could huge shots of heroin combined with a baseball bat to the head be equally effective? Ketamine-receiving patients say [just stares at the wall].

...and

Ketamine Is the World’s Dumbest Drug

. . .

The '90s were a lot of fun the first time around, and there were tons of great things about the decade. We even did a lot of wonderful, powerful, mind-altering substances... K was not one of them. K was a stupid mistake. Even a bigger mistake than Fat Boy Slim, P.L.U.R., and a strange affection for Ring Pops at the age of 20. It was one of the few things I look back on and think, "Man, that was really, really dumb. Why did we ever do that?" If the '90s are going to come back, take this lesson from someone who really enjoyed the first time around—leave the K for the cats.

Finally, I just have to say one thing about this clinical trial on Ketamine For Suicidal Ideation at Mount Sinai. The only primary and secondary outcome measures are at 24 hours post infusion? Really?? You're not following up the patients to see if they're still suicidal a week later, let's say? Is that so difficult?


(2) LiveScience declared that Family's Mental Disorders May Shape Your Interests, and Medical Xpress carried this understated story:

Survey suggests family history of psychiatric disorders shapes intellectual interests

A hallmark of the individual is the cultivation of personal interests, but for some people, their intellectual pursuits might actually be genetically predetermined. Survey results published by Princeton University researchers in the journal PLoS ONE suggest that a family history of psychiatric conditions such as autism and depression could influence the subjects a person finds engaging.

Genetically predetermined? Really? Eighteen year old Princeton freshman provide expert psychiatric diagnoses of their relatives, declare their intended majors, and somehow manage to confirm the 'tortured alcoholic artist' and 'autistic engineer' stereotypes (Campbell & Wang, 2012). Surprise!

But the basic premise of asking 18 yr olds for valid psychiatric diagnoses of family members might be flawed, you say? Neuroskeptic posted on this paper, but not skeptically enough, in my view. I would go directly to this comment by Professor Keith R Laws:

Obviously there are a few issues with such studies:
1) the ability of individuals to report accrurately - it seems for example that they viewed propsopagnosia as a memory disorder - so they are not identifying at all accurately (at least for some conditions)
2) there seem to be strong oddities in the incidence rates e.g. schizophrenia
3) in the latter case, there may be a strong social desirability effect
4) indeed, in relation to desirability, such individuals may be more prone to endorse stereotypes (of autism-geek etc)
5) comorbidities were not apparently evaluated e.g. about a third of all people with autism have a comorbid disorder; similarly with other disorders esp things such as OCD (with sz etc)

And it's really stretching it to say anything at all about genetics from a survey (Campbell & Wang, 2012):

Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests.

Moving right along...


(3) Mail Online screamed that Every textbook on the brain is wrong - and our brains are more similar to monkeys than we thought. Did you know that Wernicke's area has moved? Wow, only 12 yrs after the pioneering PET/fMRI studies on speech perception by Scott et al. (2000) and Binder et al. (2000)? It seems to me that the authors of the paper in question (DeWitt & Rauschecker, 2012) were not at all shy about taking credit for this seemingly historical change in human neuroanatomy. Some choice quotes from the Mail Online article:

But, now, research that analyzed more than 100 imaging studies concludes that Wernicke's area is in the wrong location.

The site [not so] newly identified is about 3 centimeters closer to the front of the brain and on the other side of auditory cortex — miles away in terms of brain architecture and function.

The finding, published online this week in the Early Edition of the Proceedings of the National Academy of Sciences (PNAS), means that ‘textbooks will now have to be rewritten,’ says the study's senior author, Josef Rauschecker, Ph.D., a professor in the department of neuroscience at Georgetown University Medical Center (GUMC).

‘We gave old theories that have long hung - a knockout punch,’ says Rauschecker...

‘If you Google 'language organization in the brain,' probably every cartoon illustration out there is wrong,’ says lead author Iain DeWitt, a Ph.D. candidate in Georgetown's Interdisciplinary Program in Neuroscience.

This was all the more curious because the term "Wernicke's area" did not appear once in the original PNAS paper. I might get around to posting on this topic, but (even if I do) it's better to read Professor Sophie Scott's post, Wernicke's area: are we still looking for it? Was it ever lost.


References

Binder JR, Frost JA, Hammeke TA, Bellgowan PS, Springer JA, Kaufman JN, Possing ET. (2000). Human temporal lobe activation by speech and nonspeech sounds. Cereb Cortex 10:512-28.

Campbell BC, Wang SS (2012). Familial Linkage between Neuropsychiatric Disorders and Intellectual Interests. PLoS One 7(1):e30405.

Dewitt I, Rauschecker JP. (2012). Phoneme and word recognition in the auditory ventral stream. Proc Natl Acad Sci Feb 1. [Epub ahead of print]

Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959-64.

Scott SK, Blank CC, Rosen S, Wise RJ. (2000). Identification of a pathway for intelligible speech in the left temporal lobe. Brain 123:2400-6.

Yang C, Zhou ZQ, Yang JJ. (2011). Be prudent of ketamine in treating resistant depression in patients with cancer. J Palliat Med. 14:537.