Neurology Center

Freud's The Interpretation of Dreams is a very long book but the essential theory is very simple: dreams are thoughts. While dreaming, we are thinking about stuff, in exactly the same way as we do when awake. The difference is that the original thoughts rarely appear as such, they are transformed into weird images.

Only emotions survived unaltered. A thought about how you're angry at your boss for not giving you a raise might become a dream where you're a cop angrily chasing a bank robber, but not into one where you're a bank robber happily counting his loot. By interpreting the meaning of dreams, the psychoanalyst could work out what the patient really felt or wanted.

The problem of course is that it's easy to make up "interpretations" that follows this rule, whatever the dream. If you did dream that you were happily counting your cash after failing to get a raise, Freud could simply say that your dream was wish-fulfilment - you were dreaming of what you wanted to happen, getting the raise.

But hang on, maybe you didn't want the raise, and you were happy not to get it, because it supported your desire to quit that crappy job and find a better one...

Despite all that, since reading Freud I've found myself paying more attention to my dreams (once you start it's hard to stop) and I've found that his rule does ring true: emotions in dreams are "real", and sometimes they can be important reminders of what you really feel about something.

Most of my dreams have no emotions: I see and hear stuff, but feel very little. But sometimes, maybe one time in ten, they are accompanied by emotions, often very strong ones. These always seem linked to the content of the dream, rather than just being random brain activity: I can't think of a dream in which I was scared of something that I wouldn't normally be scared of, for example.

Generally my dreams have little to do with my real life, but those that do are often the most emotional ones, and it's these that I think provide insights. For example, I've had several dreams in the past six months about running; in every case, they were very happy ones.

Until several months ago I was a keen runner but I've let this slip and got out of shape since. While awake, I've regretted this, a bit, but it wasn't until I reflected on my dreams that I realized how important running was to me and how much I regret giving it up.

While awake, we're always thinking about things on multiple levels: we don't just want X, we think "I want X" (not the same thing), and then we go on to wonder "But should I want X?", "Why do I want X?", "What about Y, would that be better?", etc. Thoughts get piled up on top of one another: it's all very cluttered.

In a dream, most of the layers go silent, and the underlying feeling comes closer to the surface. The principle is the same, in many ways, as this.

But how do I know that feelings in dreams are the "real" ones? In most respects, dreams are less real than waking stuff: we dream about all kinds of crazy stuff. And even if we accept that dreams offer a window into our "underlying" feelings, who's to say that deeper is better or more real?

Well, "buried" feelings matter whenever they're not really buried. If a desire was somehow "repressed" to the point of having no influence at all, it might as well not exist. But my feelings about running were not unconscious as such - I was aware of them before I had these dreams - but I was "repressing" them, not in any mysterious sense, but just in terms of telling myself that it wasn't a big deal, I'd start again soon, I didn't have time, etc.

The problem was that this "repression" was annoying, it was causing long-term frustration etc. In dreams, all of these mild emotions spanning several months were compressed into powerful feelings for the duration of the dream (a few minutes, although the dreams "felt like" they lasted hours).

Overall, I don't think it's possible or useful to interpret dreams as metaphorical representations in a Freudian sense (a train going into a tunnel = sex, or whatever). I suspect that dreams are more or less random activity in the visual and memory areas of the brain. But that doesn't mean they're meaningless: they're activity in your brain, so they can tell you about what you think and feel.

There are three basic schools of thought on the Israel / Palestine thing.

• Those evil Israelis are out to destroy Palestine, and the Palestinians are just fighting back.
• Those evil Palestinians are out to destroy Israel, and the Israelis are just fighting back.
• It's a cycle of violence, where both sides are fighting back against the other.
  

the number of Qassams fired increases by 6% on the first day after a single killing of a Palestinian by Israel; the probability of any Qassams being fired increases by 11%; and the probability of any Israelis being killed by Palestinians increases by 10%. Conversely, 1 day after the killing of a single Israeli by Palestinians, the number of Palestinians killed by Israel increases by 9%, and the probability of any Palestinians being killed increases by 20%

....retaliation accounts for a larger fraction of Palestinian compared with Israeli aggression: in the levels specification, 10% of all Qassam rockets can be attributed to prior Israeli attacks on Palestinians, but only 4% of killings of Palestinians by Israel can be attributed to prior Palestinian attacks on Israel.... 6% of all days on which Palestinians attack Israel with rockets, and 5% of all days on which they attack by killing Israelis, can be attributed to retaliation; in contrast, this is true for only 2% of all days on which Israel kills Palestinians.

Over one half of Israelis and three quarters of Palestinians think the other side seeks to take over their land. When accounting for their own acts of aggression, Israelis often claim to be merely responding to Palestinian violence, and Palestinians often see themselves as simply reacting to Israeli violence.

You've got an idea: a new way of doing things; a change; a paradigm shift. It might work, it might be no better than what we've got already, or it might end up being a disaster.

The honest way to present your proposal would be to admit its novelty, and hence the uncertainty: this is a new idea I had, I can't promise anything, but here are my reasons for thinking it's worth a try, here are the likely costs and benefits, here are the alternatives.

However, let's suppose you don't want to do that. That's hard work, and if your idea is crap, people could tell. How else could you convince them? By making it seem as though it's not a new idea at all.

You could dress your idea up as:

• the glorious past. Your idea is nothing more than how we did things back in the golden age, when everything was great. For some reason, people strayed from the true path, and things went bad. We should go back to the the good old days. It worked then, so it'll work now. You'll use words like: restoring, reviving, regaining, renewing... "re" is your friend.
• the next step. Your idea is just the logical progression of what we're already doing. Things used to be bad, and then they started to change, and get better. Let's make them even better, by doing more of the same. It's inevitable, anyway: you can't stop history. You'll use words like: progress, forward, advance, build, grow...
  
• catching up. You're just saying we should bring stuff into line with the way things are done elsewhere, which as we know, is working well. It's not even a matter of moving forward, so much as keeping up. It would be weird not to change. We don't want to be dinosaurs. You'll use words like: modernization, rationalization, reform...
  
• keeping things the same. Things are fine right now, and don't need improving. But in order for things to stay great, we must adapt to changing circumstances, so we'll have to make a few adjustments, but don't worry, fundamentally things are going to stay just as they are. You'll use words like: preserving, maintaining, protecting, upholding, strengthening...

The first direct evidence of a genetic link to attention-deficit hyperactivity disorder has been found, a study says.

Only 57 out of the 366 children with ADHD had the genetic variant supposed to be a cause of the illness. That would suggest that other factors are the main cause in the vast majority of cases. Genes hardly explain at all why some kids have ADHD and not others.

the findings allow us to refute the hypothesis that ADHD is purely a social construct, which has important clinical and social implications for affected children and their families.

An unusually gripping genetics paper from Biological Psychiatry: Pagnamenta et al.

The authors discuss a family where two out of the three children were diagnosed with autism. In 2009, they detected a previously unknown copy number variant mutation in the two affected brothers: a 594 kb deletion knocking out two genes, called DOCK4 and IMMP2L.

Yet this mutation was also carried by their non-autistic mother and sister, suggesting that it wasn't responsible for the autism. The mother's side of the family, however, have a history of dyslexia or undiagnosed "reading difficulties"; all of the 8 relatives with the mutation "performed poorly on reading assessment".

Further investigation revealed that the affected boys also carried a second, entirely separate, novel deletion, affecting the gene CNTNAP5. Their mother and sister did not. This mutation came from their father, who was not diagnosed with autism but apparently had "various autistic traits".

Perhaps it was the combination of the two mutations that caused autism in the two affected boys. The mother's family had a mutation that caused dyslexia; the father's side had one that caused some symptoms of autism but was not, by itself, enough to cause the disorder per se.

However, things aren't so clear. There were cases of diagnosed autism spectrum disorders in the father's family, although few details are given and DNA was only available from one of the father's relatives. So it may have been that the autism was all about the CNTNAP5, and this mutation just has a variable penetrance, causing "full-blown" autism in some people and merely traits in others (like the father).

In order to try to confirm whether these two mutations do indeed cause dyslexia and autism, they searched for them in several hundred unrelated autism and dyslexia patients as well as healthy controls. They detected the a DOCK4 deletion in 1 out of 600 dyslexics (and in his dyslexic father, but not his unaffected sister), but not in 2000 controls. 3 different CNTNAP5 mutations were found in the affected kids from 3 out of 143 autism families, although one of them was also found in over 1000 controls.

This is how psychiatric genetics is shaping up: someone finds a rare mutation in one family, they follow it up, and it's only carried by one out of several hundred other cases. So there are almost certainly hundreds of genes "for" disorders like autism, and it only takes a mutation in one (or two) to cause autism.

Here's another recent example: they found PTCHD1 variants in a full 1% of autism cases. It seems to me that autism, for example, is one of the things that happens when something goes wrong during brain development. Hundreds of genes act in synchrony to build a brain; it only takes one playing out of tune to mess things up, and autism is one common result.

Mental retardation and epilepsy are the other main ones, and we know that there are dozens or hundreds of different forms of these conditions each caused by a different gene or genes. The million dollar question is what it is that makes the autistic brain autistic, as opposed to, say, epileptic.

The "rare variants" model has some interesting implications. The father in the Pagnamenta et al. study had never been diagnosed with anything. He had what the authors call "autistic traits", but presumably he and everyone just thought of those as part of who he was - and they could have been anything from shyness, to preferring routine over novelty, to being good at crosswords.

Had he not carried the CNTNAP5 mutation, he'd have been a completely different person. He might well have been drawn to a very different career, he'd probably never have married the woman he did, etc.

Of course, that doesn't mean that it's "the gene for being him"; all of his other 23,000 genes, and his environment, came together to make him who he was. But the point is that these differences don't just pile up on top of each other; they interact. One little change can change everything.

Link: BishopBlog on why behavioural genetics is more complicated than some people want you to think.

Pagnamenta, A., Bacchelli, E., de Jonge, M., Mirza, G., Scerri, T., Minopoli, F., Chiocchetti, A., Ludwig, K., Hoffmann, P., & Paracchini, S. (2010). Characterization of a Family with Rare Deletions in CNTNAP5 and DOCK4 Suggests Novel Risk Loci for Autism and Dyslexia Biological Psychiatry, 68 (4), 320-328 DOI: 10.1016/j.biopsych.2010.02.002

People who quit antidepressants slowly, by gradually decreasing the dose, are much less likely to suffer a relapse, according to Baldessarini et al. in the American Journal of Psychiatry.

They describe a large sample (400) of patients from Sardinia, Italy, who had responded well to antidepressants, and then stopped taking them. The antidepressants had been prescribed for either depression, or panic attacks.

People who quit suddenly (over 1-7 days) were more likely to relapse, and relapsed sooner, than the ones who stopped gradually (over a period of 2 weeks or more).

This graph shows what % of the patients in each group remained well at each time point (in terms of days since their final pill.) As you can see, the two lines separate early, and then remain apart by about the same distance (20%) for the whole 12 months.

What this means is that rapid discontinuation didn't just accelerate relapses that were "going to happen anyway". It actually caused more relapses - about 1 in 5 "extra" people. These "extra" relapses all happened in the first 3 months, because after that, the slope of the lines is identical.

On the other hand, they rarely happened immediately - it's not as if people relapsed within days of their last pill. The pattern was broadly similar for older antidepressants (tricyclics) and newer ones (SSRIs).

The authors note that these data throw up important questions about "relapse prevention" trials comparing people who stay on antidepressants vs. those who are switched - abruptly - to placebo. People who stay on the drug usually do better, but is this because the drug works, or because the people on placebo were withdrawn too fast?

This was an observational study, not an experiment. There was no randomization. People quit antidepressants for various "personal or clinical reasons"; 80% of the time it was their own decision, and only 20% of the time was it due to their doctor's advice.

So it's possible that there was some underlying difference between the two groups, that could explain the differences. Regression analysis revealed that the results weren't due to differences in dose, duration of treatment, diagnosis, age etc., but you can't measure every possible confound.

Only randomized controlled trials could provide a final answer, but there's little chance of anyone doing one. Drug companies are unlikely to fund a study about how to stop using their products. So we have only observational data to go on. These data fit in with previous studies showing that there's a similar story when it comes to quitting lithium and antipsychotics. Gradual is better.

But that's common sense. Tapering medications slowly is a good idea in general, because it gives your system more time to adapt. Of course, sometimes there are overriding medical reasons to quit quickly, but apart from in such cases, I'd always want to come off anything as gradually as possible.

Baldessarini RJ, Tondo L, Ghiani C, & Lepri B (2010). Illness risk following rapid versus gradual discontinuation of antidepressants. The American journal of psychiatry, 167 (8), 934-41 PMID: 20478876

There's a paradox at the heart of modern psychiatry, according to an important new paper by Dr Charles E. Dean, Psychopharmacology: A house divided.

It's a long and slightly rambling article, but Dean's central point is pretty simple. The medical/biological model of psychiatry assumes that there are such things as psychiatric diseases. Something biological goes wrong, presumably in the brain, and this causes certain symptoms. Different pathologies cause different symptoms - in other words, there is specificity in the relationship between brain dysfunction and mental illness.

Psychiatric diagnosis rests on this assumption. If and only if we can use a given patient's symptoms to infer what kind of underlying illness they have (schizophrenia, bipolar disorder, depression), diagnosis makes sense. This is why we have DSM-IV which consists of a long list of disorders, and the symptoms they cause. Soon we'll have DSM-V.

The medical model has been criticized and defended at great length, but Dean doesn't do either. He simply notes that modern psychiatry has in practice mostly abandoned the medical model, and the irony is, it's done this because of medicines.

If there are distinct psychiatric disorders, there ought to be drugs that treat them specifically. So if depression is a brain disease, say, and schizophrenia is another, there ought to be drugs that only work on depression, and have no effect on schizophrenia (or even make it worse.) And vice versa.

But, increasingly, psychiatric drugs are being prescribed for multiple different disorders. Antidepressants are used in depression, but also all kinds of anxiety disorders (panic, social anxiety, general anxiety), obsessive-compulsive disorder, PTSD, and more. Antipsychotics are also used in mania and hypomania, in kids with behaviour problems, and increasingly in depression, leading some to complain that the term "antipsychotics" is misleading. And so on.

So, Dean argues, in clinical practice, psychiatrists don't respect the medical model - yet that model is their theoretical justification for using psychiatric drugs in the first place.

He looks in detail at one particularly curious case: the use of atypical antipsychotics in depression. Atypicals, like quetiapine (Seroquel) and olanzapine (Zyprexa), were originally developed to treat schizophrenia and other psychotic states. They are reasonably effective, though most of them are no more so than older "typical" antipsychotics.

Recently, atypicals have become very popular for other indications, most of all mood disorders: mania and depression. Their use in mania is perhaps not so surprising, because severe mania has much in common with psychosis. Their use in depression, however, throws up many paradoxes (above and beyond how one drug could treat both mania and its exact opposite, depression.)

Antipsychotics block dopamine D2 receptors. Psychosis is generally considered to be a disorder of "too much dopamine", so that makes sense. The dopamine hypothesis of psychosis and antipsychotic action is 50 years old, and still the best explanation going.

But depression is widely considered to involve too little dopamine, and there is lots of evidence that almost all antidepressants (indirectly) increase dopamine release. Wouldn't that mean that antidepressants could cause psychosis (they don't?). And why, Dean asks, would atypicals, that block dopamine, help treat depression?

Maybe it's because they also act on other systems? On top of being D2 antagonists, atypicals are also serotonin 5HT2A/C receptor blockers. Long-term use of antidepressants reduces 5HT2 levels, and some antidepressants are also 5HT2 antagonists, so this fits. However, it creates a paradox for the many people who believe that 5HT2 antagonism is important for the antipsychotic effect of atypicals as well - if that were true, antidepressants should be antipsychotics as well (they're not.) And so on.

There may be perfectly sensible answers. Maybe atypicals treat depression by some mechanism that we don't understand yet, a mechanism which is not inconsistent with their also treating psychosis. The point is that there are many such questions standing in need of answers, yet psychopharmacologists almost never address them. Dean concludes:

it seems increasingly obvious that clinicians are actually operating from a dimensional paradigm, and not from the classic paradigm based on specificity of disease or drug... the disjunction between those paradigms and our approach to treatment needs to be recognized and investigated... Bench scientists need to be more familiar with current clinical studies, and stop using outmoded clinical research as a basis for drawing conclusions about the relevance of neurochemical processes to drug efficacy. Bench and clinical scientists need to fully address the question of whether the molecular/cellular/anatomical findings, even if interesting and novel, have anything to do with clinical outcome.