My last post wore me out, emotionally and physically, so I’ve needed a break. But here I sit again, ready to write. The prior essay centered on structural changes in synapses, and how those relate to difficulties with changes in either behavior or medications. Loss of serotonin receptors following SSRI antidepressant use (e.g. Prozac), leads to a dependence on the medication. When SSRIs are withdrawn, the brain no longer has the receptor capacity to work with the lowered serotonin level which follows. So we get depressed. I have experienced this repeatedly in my efforts to lower my antidepressant load.

The brain gets used to certain inputs. Many pleasurable activities and drugs of abuse increase dopamine. Like serotonin, dopamine is a neurotransmitter used by a minute fraction of the brain’s neurons. When the nucleus accumbens, or ‘pleasure center’, gets flushed with this chemical, one feels deep satisfaction, sensual gratification, or even euphoria. Later, when dopamine levels drop, one may develop a desperate craving to get another burst of it. Hence: addiction. Possibly behaviors that lead to unpleasant moods, like isolating or ruminating on worries and problems, provide short term release of neurotransmitters that our brains ‘like’, even though the end result is depression. This portrayal simplifies the situation, like describing an epic film with one paragraph. But my point is just that on some level much of how we feel, and what we think or do, comes from shifting movements in the symphony of chemical interactions in the brain.

So what does this all say about human nature? Are we ‘nothing’ but conglomerations of proteins, neurotransmitters, and other biological molecules? In the last post I also mentioned Jeffrey Schwartz, MD, and his hypothesis that in addition to neurons and associated brain cells, our minds consist of something non-material, which he calls ‘mental force’. This entity could just as well be called our ‘soul’, since he believes it determines our decisions under the principle of free will.

I don’t accept this proposal. Not because I think free will is an illusion, or because I don’t believe in souls. I have conviction that both exist and are the vital organs of human life. My opinion, however, is that both human ‘spirit’ and ‘will’ arise from the matrix of matter itself. The intricate and finely woven fabric of our brains makes freely determined decisions, and houses our divine spark. Humans look for miracles, yet all the time we seek them we are living in their midst. Not only that, but each one of us is divine in every sense of the word. We don’t need to postulate some ethereal force that exists detached from the trillions of cells, each a tiny universe of activity, which have grown in unison and become the mysteries we call bodies. God does not need to speak outside of matter, because our atoms and molecules already sing God’s song.

Even with the above proviso, I suspect that my spiritual ideas do not particularly interest those who visit this blog. So I’ll stop here with the philosophy. I only want to convince readers that whether by taking medications or changing our behaviors, we are tinkering with the intimate particles of our being. However, the two approaches (drugs and action) differ as coal differs from diamonds. They may be in the same category on some molecular level, but they diverge in beauty and endurance. Ingesting a chemical to improve one’s experience is akin to to reshaping an ice sculpture with a blow torch. The tool carries too much power, and acts too crudely to result in anything fine. “If you can’t feel better, drugs at least make you feel different.” At the price of (possibly) lifelong dependence on psychiatric chemicals, one (typically) gains a few months of relief from pain. Then, all too often, the pain returns. Only now depression comes encumbered with an addiction (what else to call it?) to drugs that no longer work. Stopping medications takes one from depression into the pounding heart of hell.

Much better to work on meditating, improving spiritual sensitivity, exercising, and adjusting thought habits. Maybe drugs can help for a little while. If so, doctors should remain ever-vigilant for the first opportunity to start withdrawing them. Let us use finesse to chip and carve the ice that encases our moods. Take our time and work hard, and we can sculpt our depression into tragic but nonetheless beautiful memories.

I guess this is a repeat of my last message. Hopefully, since it is (a little) shorter, it will be more widely read. I yearn for it to help someone. This kind of thinking comes too late for me. I am already addicted to psychiatric medications and must struggle my way free. This writing project would fulfill both my spirit and my will if a recently diagnosed reader found it useful, and if it bolstered a non-medicated regimen of mood care. If you are that reader, I pray that the uncountable molecules of your brain begin to dance in harmony. I have faith that you will choreograph a lasting peace.

Today, my decision about topics comes down to two choices, both born of recent posts or replies to comments: 1) Bad Thought and Behavior Habits and how hard it is to change them; or 2) Discontinuing Psychiatric Drugs and how it is made difficult by receptor downregulation. The first has to do with why I often ignore the things that have been taught to me about how to be healthy. The second is about why I get so depressed when I try to stop (e.g.) Cymbalta. Then I realized that the two are related. They both have to do with fixed patterns of response in the brain. So this essay deals with both those issues. It is long (despite my resolution to keep posts under 500 words), and involves some physiology. But I think the connection between habits, drugs, and changes in the brain lies at the heart of many difficult emotional problems.

Of course, science understands drugs better than habits. When a negative behavior becomes habitual, so that we repeatedly cave in to it rather than do the harder thing that will make us feel better in the long run, millions (or billions) of cells across the brain may get involved. Many complicated neural centers of thought and action determine such bad habits. On the other hand, when our brains become habituated to the effects of psychiatric medications, the problem largely can be explained by changes in the levels of one or a few proteins. Since I know little about the psychology behind habits and resistance to change, most of this post will focus on receptors. I will try to draw (hopefully not make up) parallels between the brain’s adjustment to pharmaceuticals and its development of habits.

Many people on psychiatric medications have found that a drug may improve ‘symptoms’ after a few weeks, but then gradually works less and less well. This happens, in part, because the body reduces the number of receptor-proteins that respond to that drug, or to one of the natural chemicals the drug increases.

I started my medication odyssey with Prozac (fluoxetine). This drug blocks the removal (reuptake) of serotonin from the synapses in parts of the brain that use serotonin as a signalling molecule. The synapse is the small area that separates the pre-synaptic cell that sends a signal, in this case one carried by serotonin, from the post-synaptic cell that receives it. Removing the released serotonin from the space between the cells–the synapse–attenuates the message, so that it is time-limited, and doesn’t just go on ‘forever’. Since compared to earlier antidepressants Prozac is relatively selective in blocking reuptake of serotonin–but not other transmitters, it is an example of the SSRI class: Selective Serotonin Reuptake Inhibitors.

Under normal circumstances, the pre-synaptic cell releases serotonin, but then sucks it back out of the synapse using ‘reuptake’ proteins. Without the reuptake mechanism, serotonin would persist in the cleft for much longer times, and at higher concentrations, than normal. In fact, Prozac accomplishes exactly that: it blocks the reuptake protein and so causes an increase in synaptic serotonin.

As an aside, only about one-thousandth of one percent of brain nerve cells use serotonin to send signals. Despite their small numbers, serotonin neurons affect many different parts of the brain. That explains, in part, why they have unwanted side effects: areas of the nervous system we’d rather not mess with (like parts mediating sexual response) are modulated by serotonin, just like the parts that alter moods. Another important point is that to date there is no evidence that depression results from an actual deficiency in serotonin levels, even though increasing serotonin activity does elevate moods.

So why does Prozac often quit working over time? In part, it may be because the cells respond to abnormal increases in serotonin by reducing the number of post-synaptic receptors for that transmitter. It’s kind of like what happens with noise. If you want to hear something really faint, like a soft whisper, you cup your hand behind your ear to increase your ability to make out the words. As the person speaks louder, you remove your hand because it’s not so hard to detect their voice anymore. If they start yelling, you might even plug your ears to tone down the volume. The post-synaptic neuron that detects the serotonin signal no longer has to listen so hard. So it reduces the number of proteins in its cell membrane that ‘hear’ the serotonin molecule. And the drug that increases serotonin, and that once had terrific effectiveness, now has less.

Naturally, there are complicating factors. For instance, Prozac may have an immediate stimulating effect, but much of its antidepressant activity is delayed by several weeks. This is thought to be due to changes in receptor numbers on the pre-synaptic cell. I won’t go into this wrinkle, because it does not change the basic fact that eventually serotonin levels increase, and that soon after the system adjusts to the elevated transmitter levels. Regardless of the details, the end result is that the brain settles back toward its natural state. It adapts to the increase in transmitter by reducing its sensitivity.

What happens when you stop the Prozac? At this point, your neurons are accustomed to increased serotonin levels. What was once abnormally high is now, according to your brain, the right amount. When you take the (reuptake inhibiting) drug away, reuptake goes back up, which (probably along with other changes) reduces synaptic serotonin. Since the brain has adapted to high serotonin, this reduction (back to levels that once were normal) feels like a deficiency. The serotonin system is under-stimulated, and you feel depressed. And because serotonin neurons are so widespread, other withdrawal symptoms are not uncommon. You might even be more depressed than when you first started Prozac. If you can weather the depression without killing yourself, there is a pretty good chance that your neurons will return to their original condition. Or maybe not. There is also a risk that not all of the changes are reversible. One line of evidence that suggests receptor downregulation may sometimes be irreversible comes from the fact that some people have long-term sexual dysfunction that continues after SSRI agents have been discontinued.

Either way, the habituation of your brain to the presence of Prozac (and other SSRIs) makes it a difficult drug to stop. The same thing happens with heroin users: the number of opiate receptors drops, and the addict feels horrible if her or she can’t get enough heroin. (In the brain, ‘opiate’ receptors normally detect peptides called endorphins; heroin and related drugs stimulate those receptors and thereby promote analgesia and euphoria.) Hence they have trouble springing back from ‘receptor downregulation’ just like Prozac users. A common name for this is ‘addiction’. For obvious reasons, drug companies and psychiatrists resist applying this term to the withdrawal symptoms people have when psychiatric drugs like SSRIs are stopped.

Now, back to habits. Could it be that similar adaptations to signal strength, protein levels, and other features in various parts of the brain account for why habits are so hard to break? When we try to alter our behavior away from the established pattern, do we experience a seeming deficit in some chemical important to feelings of well-being? This mechanism must be operative in bad habits involving substance abuse, like cigarette addiction. But would it be extending the analogy too far to suggest it explains my habit of retreating into depression after minor setbacks? Or how I avoid doing the things that I know will gradually lead to less depression (e.g., distraction, exercise, positive self-talk), and instead curl up in a darkened room because it somehow feels better at that moment?

To answer that, one confronts the question of whether all of our decisions result from neuronal activity. Surprisingly (to me) not all scientists agree with that notion, or at least not entirely. Jeffrey Schwartz, MD, published a book in 2002 with reporter Sharon Begley called, The Mind and Brain: Neuroplasticity and the Power of Mental Force. In it, he uses obsessive-compulsive disorder (OCD) as a model for how the mind and brain interact. On the one hand, he reports that PET imaging data imply that OCD results from faulty action patterns in the frontal lobe. he goes on to show how entraining OCD patients (via CBT techniques) with new behaviors changes those circuits, and that the better the patients become, the ‘better’ the circuits look. This supports the idea that bad habits can result from changes in neuronal circuitry (note that OCD behaviors are particularly bad and pernicious; I want to reassure OCD sufferers that I am not saying their condition is something you can just ‘quit’ like cigarette smoking–hard as that is).

(Note: these images taken from the site linked by clicking on them. They were not obtained via CC license. Since they are promotional pictures on an OCD clinic’s website, and this is a mental health blog, I assume the developers would not mind. I do not have any affiliation with that organization, by the way.)

Schwartz also conveys the optimistic message that with training and intention we can change cellular connections. In other words, we can physically alter our brains to improve our lives (which brings up the giant topic of neuroplasticity, a subject for another blog). So Schwartz agrees that structural and functional elements in the brain determine habits, and that changing those elements is the key to improvement.

On the other hand, however, he argues that the intention to change behavior (and hence the brain), originates from something outside the physical structure of the nervous system: a so-called ‘mental force’. He is doing nothing less than postulating a new physical entity to add to the nuclear strong, nuclear weak, electromagnetic and gravitational forces already known by physicists. His argument is well-constructed, though it fails to convince me. (That does not mean I don’t believe in forces outside of matter, only that his reasoning and supporting data are insufficient to establish non-material forces acting in this instance.)

Whether intention originates in neuronal tissue or outside of it, it is nevertheless clear that behavior is grounded in the brain, that we can and often do change our behavior, and that doing so probably involves changing the structure and/or function of neural circuits. My whole reason for this long discussion is to make the point that while drugs quickly and efficiently change synapses and brain circuits, we can do the same thing (more slowly) with willpower, training, and practice. Breaking the habits that promote depression is then not all that different from recovering from long-term use of psychiatric drugs, although it is probably easier. In both instances we need to readjust synaptic activity.

Cognitive research has shown that to some extent persistent depression is about bad habits of thought and action. If we can break those habits, we can reduce depression. It may even be that improving thought and behavior increases brain serotonin activity, just like Prozac. However, unlike using a synthetic drug, in this case the neurotransmitter gets increased in just the right locations, not the whole brain. There is no problem with, for instance, anorgasmia or weight gain. We can accomplish the same thing as drugs, but without the side effects. It just takes the desire to change, and enough motivation to step off the easy and well-worn path. One needs to muster the courage to forge new trails and conquer new horizons. But drugs are not required.

Medications all-too-often only provide temporary relief. In some cases, a period of drug-mediated improvement in depression can give one the solid ground needed to step in a new direction. After that, the ideal decision would be to withdraw the drug in short order. I believe medications can play a useful, even vital role. But pharmaceutical agents can not, and should not be the only compass used to find a new way to live. Lifelong treatment with psychiatric medications is questionable, and despite what we are led to believe, most pharmaceutical agents lack scientific evidence of usefulness over long term treatment. So if drugs are used at all, they should be used in the lowest number, at the lowest doses, and for the shortest time possible. It takes much effort and time to change neural pathways without drugs, but the improvement is longer lasting, without side effects, and far more natural.

What does it take to transfer understanding in the rational part of the brain to the emotional part? The number of years I’ve spent in therapy, or support groups, is vast. Here’s a partial list of the therapy:

And here’s a partial list of the support groups:

Now, you would think that after all that I would not spin out because my blog-stats dropped. But I did. So how do I take all the knowledge that I really do have about codependence, abandonment issues, self-esteem, acceptance, etc, and make myself well? How come it is so easy to know something with my mind but remain completely clueless in my heart? Is there anyway to transfer the knowledge? Can I build some kind of high-speed data connection between the two parts of my brain that deal with these things? (Aside: Don’t you just hate brain/computer comparisons?)

The only solution I can find is looking for improvement (‘progress, not perfection’ is what they say in AA). Yes, I did crash and burn about the web statistics, but I pulled myself out of it pretty quickly. I was even able to see the humor in my response. That is much better than ever before. What’s more, I opened up about what was going on with me, reached out for help, and was rewarded by many kind messages from those who’ve been reading my posts. (And this was true even though I’ve only been doing this with any regularity for 3-4 weeks; a real testament to the kindness of those who read mental health blogs.)

Thus, I look for signs that my emotional skills today are more honed than yesterday. But I am still puzzled about why I’m so dense. Therapy ‘should’ help the emotions. The unconscious ‘ought’ to learn, but mine obviously did not. Or maybe it sometimes learns, but other times forgets. One way or the other, I find my theoretical understanding far surpasses my practical application of what I know about how to be healthy. Hence, I find it easier to give advice than to live in a state of emotional balance and spiritual connection. It would be easy to blog about all the stuff I’ve been told, and never mention that it only works for me half the time. But that would not be honest, or fair, or helpful to others or to me. So here I am, admitting that the simplest things still trip me up, even though I was fortunate enough to have good insurance, the resources to pay for what insurance would not, and to live in an area with a surfeit of recovery and therapy groups.

I’ll end by asking if anyone knows some tricks for taking cognitive understanding, and turning it into emotional maturity. I am anxious to grow out of this phase and into something more enduringly healthy.