How to Become Smarter (33 page)

In conclusion, the ability to lower one’s mood when necessary may give a person greater control over his/her emotional state and thus may improve emotional intelligence. Sections that follow describe the opposite approach, which lifts internal mood when necessary.

A clarification is necessary at this point as to what “internal mood” means. Internal mood is how a person feels mentally, as opposed to what the person shows to other people. For example, a person can feel miserable (depressed internal mood) and laugh at the same time. Conversely, it is possible to be in a state of euphoria (internal mood is elevated) but appear unemotional outwardly. Based on my self-experimentation, all treatments described in this chapter have reliable effects on internal mood, but they have inconsistent effects on external mood.

• Cooked meat can lower mood and increase fatigue, whereas cooked grains can slow down mental processes.
  
• These effects may be due to certain chemicals that form during cooking of these foods. Hard evidence at realistic doses is lacking.
  
• Cooking meat and grains at moderate temperatures (boiling or steaming) forms these chemicals in
  negligible
  amounts. Therefore, with boiled food, these chemicals should not be a cause for concern because at this dose they cannot have negative effects on physical health. They may have subtle effects on mental state.
  
• Slowing, fatigue, and low mood represent major symptoms of clinical depression. The diet rich in cooked meat and nuts and devoid of dairy may serve as an experimental model of mild depression.
  
• The depressant diet consists of cooked meat, cooked grains, nuts, fruits, and vegetables. Although low mood and slowing may seem undesirable, the depressant diet is useful in some situations and improves sleep.
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Scientists have proposed a number of different theories over the last half a century to explain the biological basis of clinical depression. This section discusses a little bit of neuroscience in relation to depression and regulation of mood. (Readers can skip the technical details and read the key points later. To jump to the second half of this section, press the skip button or
this link
.) You can refresh your knowledge of the basics of neuroscience by reading Wikipedia articles “neuron” and “chemical synapse.”

Neurotransmitters
are special chemicals that nerve cells (neurons) use for communicating with each other. When one neuron sends an electrical impulse to another neuron, the first neuron releases molecules of a neurotransmitter at the connection point between the two neurons (called a
synapse
). When the target neuron “receives” the neurotransmitter molecules, this event triggers a firing of the recipient neuron, which in turn, sends the electrical impulse on to other neurons. The whole process is rapid and takes place within a tiny fraction of a second. This is a simplified picture. In actuality, the connection between the neurons can also be inhibitory. This means that the receipt of the neurotransmitter by the target neuron will
suppress
its firing activity. Each neuron can receive signals from many neurons and can transmit signals to many neurons simultaneously. The summation of all received signals, both inhibitory and excitatory, determines whether the neuron will fire an electrical impulse (called an
action potential
) or not. Each neuron usually uses only one type of neurotransmitter to transmit electrical impulses to other neurons. The neuron is called by the name of the neurotransmitter that it uses. For example, a
serotonergic
neuron uses serotonin to send electrical impulses to other neurons. Before a neuron sends the signal, it accumulates molecules of the neurotransmitter within its axon at the connection point (
synapse
) with the recipient neuron. Sometime later, the neuron fires a signal and releases the neurotransmitter into the tiny gap between the neurons (
synaptic cleft
). After that, this signaling neuron absorbs the molecules of the neurotransmitter for future use (“takes them back” from the synaptic cleft). This process is called
reuptake
. The reuptake removes the neurotransmitter from the synaptic cleft and thus terminates the transmission of the electrical impulse. If we suppress the process of reuptake (for example, by means of special drugs), then the neurotransmitter will remain in the synaptic cleft. The “strength” of the transmitted signal will increase. If a neuron releases a greater than usual quantity of a neurotransmitter into the synaptic cleft, then the strength of the transmitted signal will also be greater. Conversely, if a neuron releases a smaller than usual amount of a neurotransmitter into the synaptic cleft, then the strength of the signal will be lower. If intracellular stores of the neurotransmitter are depleted within the sending neuron (there are ways of doing that), then the strength of signals that it will be sending to other neurons will be low. This is a simplified description and the matters are more complicated in reality. You do not need too many details because they can be confusing and are not necessary for the discussion below.

Going back to regulation of mood, the neurotransmitters that have received the greatest amount of attention in depression research are serotonin, norepinephrine, and dopamine. Each of these neurotransmitters derives from a single amino acid molecule and for this reason, they are called “monoamine neurotransmitters.” Brain cells synthesize serotonin from tryptophan, an essential amino acid. Brain cells can synthesize both norepinephrine (also known as noradrenaline) and dopamine from one of these two amino acids: tyrosine (a non-essential amino acid) and phenylalanine (an essential amino acid). Early experiments with a drug called reserpine, which depletes the stores of norepinephrine within neurons, revealed that this drug can induce symptoms of depression in healthy people. This and other observations led to the formulation of the “monoamine hypothesis of depression.” This theory states that depression may be the result of the shortage or insufficient activity of monoamine neurotransmitters (norepinephrine, dopamine, or serotonin) in the brain [
452
,
453
].

Pharmaceutical companies have developed a number of different drugs based on the monoamine hypothesis. Many of these drugs turned out to be effective antidepressants both in laboratory animals and in patients. Some of the well-known classes of antidepressant drugs are the following:

• monoamine oxidase inhibitors (MAOI, example:
  Nardil
  ®) increase the amount of serotonin, dopamine, and norepinephrine in the brain;
  
• serotonin-norepinephrine reuptake inhibitors (SNRI, example:
  Effexor
  ®) increase the amount and duration of stay of serotonin and noradrenaline within the synaptic cleft; this enhances signals transmitted by serotonergic and noradrenergic neurons;
  
• selective serotonin reuptake inhibitors (SSRI, example:
  Prozac
  ®) increase the amount of serotonin outside neurons (in extracellular space) and enhance serotonin activity in the brain;
  
• dopamine-norepinephrine reuptake inhibitors (DNRI, example:
  Wellbutrin
  ®) are supposed to enhance signals transmitted by dopaminergic and noradrenergic neurons.
  

From the story presented above, it may appear that science has confirmed the monoamine hypothesis beyond a doubt and solved all mysteries of depression. This is not true and some questions remain. For example, about one-third of depressed patients do not benefit from antidepressants and will have to try other treatments (psychotherapy, electroconvulsive therapy, sleep deprivation, St. John’s Wort, bright light therapy, and others). Some researchers have pointed out that the beneficial effects of antidepressants are smaller than what many people assume if we take into account
unreported
clinical trials where antidepressants were not effective [
454
]. These studies have shown that antidepressants are not much better than a placebo in patients with mild depression [
455
]. (This is the “publication bias:” it happens when investigators publish studies selectively. For instance, they publish clinical trials that have produced desirable results, while not publishing trials that have produced undesirable results.)

Another thing that is unclear is how antidepressant drugs improve depressed mood. SSRIs such as
Prozac
® increase the extracellular concentration of serotonin in the brain within 30 minutes. Yet, depressed patients start feeling better only after 2 or 3 weeks of daily doses of the antidepressant. What’s even more puzzling is that a drug with the opposite mode of action, tianeptine, which
enhances
instead of inhibiting the reuptake of serotonin, is also effective in the treatment of depression. Both SSRIs and tianeptine are more effective than a placebo, especially in severe depression [
454
,
456
].

A related issue is that a number of studies have failed to identify a “chemical imbalance” in the brains of depressed patients. For example, the brain level of serotonin in depressed patients is not different from that of healthy people [
457
]. Another question is how drugs that act on serotonin and norepinephrine can change mood. Among the three monoamine neurotransmitters, only dopamine directly participates in the regulation of mood. The brain region called “ventral striatum” is a part of the system that regulates emotions (
ventral
means “lower-frontal”). Experiments on laboratory animals and on human subjects have shown that dopamine activity in the ventral part of the striatum has rapid effects on mood. Drugs that increase dopamine activity in this area of the brain elevate mood within 30 minutes [
458
,
459
]. Drugs that inhibit dopamine activity (e.g., neuroleptics) can lower mood within hours [
460
,
461
]. In contrast, drugs with specific effects on serotonin (for example, SSRIs) or norepinephrine (NRIs) do not have immediate effects on mood. A rare exception is tianeptine, which is a selective serotonin reuptake enhancer (SSRE), and it can elevate mood in healthy subjects within hours [
391
,
392
,
462
]. Tianeptine has potential for abuse.

The euphoriant effect, i.e. elevation of mood in healthy people, is not the same as the antidepressant effect, which means improvement of mood in depressed patients. Most antidepressants have no euphoriant properties and carry negligible risk of abuse [
8
,
389
]. One possible explanation of the rapid mood-altering effect of tianeptine is that serotonergic neurons inhibit activity of the dopaminergic neurons that regulate mood. Tianeptine suppresses the activity of serotonergic neurons and thereby increases the activity of the dopaminergic neurons and this will lift the mood [
463
].

Recent studies show that some drugs that do not act on monoamine neurotransmitters can relieve depression much faster than the existing antidepressants. Intravenous infusion of ketamine, a drug that has anesthetic and hallucinogenic properties at high doses, can produce a significant clinical improvement in depressed patients within hours, not weeks [
464
]. Scopolamine, a drug for the treatment of motion sickness, can produce significant improvements within days [
465
]. These are promising studies and further research is needed to identify and validate short-acting antidepressant drugs. These developments can improve quality of life of patients and their families. In summary, there is a lot of supporting evidence but also some unresolved questions regarding the monoamine hypothesis of depression. Just to remind you, this theory suggests that depressed mood will improve if we increase the amount or activity of serotonin, noradrenaline, or dopamine in the brain.

Monoamine neurotransmitters derive from amino acids and the natural source of amino acids is dietary protein. It seems logical to hypothesize that insufficient consumption of protein is a possible cause of depression. In other words, if a person increases her consumption of protein-rich foods, this may mimic the effects of some antidepressant drugs. This diet will increase the supply of tryptophan, tyrosine, and phenylalanine and thereby will facilitate the synthesis of serotonin, noradrenaline, and dopamine in the brain. Conversely, a low-protein diet should worsen the symptoms of depression. One study supports the second part of this argument. In that study a low-protein diet enhanced depressive symptoms in laboratory rats [
466
,
1003
]. The first part of the argument—the possible antidepressant properties of a high-protein diet—is trickier.

As you may recall, in Chapter Three we talked about experiments on rats where a high-protein diet increased activity of these animals and increased the level of dopamine in the striatum [
329
,
330
]. The high-protein diet in one of those reports contained 50% casein by calories, and just to remind you, casein is a predominant protein in cow milk. Laboratories sterilize the chow for laboratory rodents by autoclaving (high-pressure steaming), but heating of dairy products does not produce any mutagens [
152
,
154
]. Cooked or pasteurized dairy does not lower mood, based on my experience and on the absence of such reports in scientific literature. Therefore, you could say that this high-casein diet is a raw high-protein diet. The chemical changes in the brains of the laboratory rats in the above studies point to the possible stimulant and euphoriant effects of this type of high-protein diet. The antidepressant effect can sometimes coincide with, but is not the same as the euphoriant and psychostimulant effects.